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Child Development. 2023;94:970–98 4.wileyonlinelibrary.com/journal/cdev
EMPI RICA L ARTICLE
Language and reading impairments are associated with increased
prevalence of non- right- handedness
FilippoAbbondanza1 | Philip S.Dale2 | Carol A.Wang3 | Marianna E.Hayiou- Thomas4 |
UmarToseeb5 | Tanner S.Koomar6 | Karen G.Wigg7 | YuFeng7 | Kaitlyn M.Price7,8 ,9 |
Elizabeth N.Kerr10,11 | Sharon L.Guger11 | Maureen W.Lovett8,10 | Lisa J.Strug12,13 |
Elsjevan Bergen14 | Conor V.Dolan14 | J. BruceTomblin6 | KristinaMoll15 |
GerdSchulte- Körne15 | NinaNeuhoff15 | AndreasWarnke16 | Simon E.Fisher17,18 |
Cathy L.Barr7,8 , 9 | Jacob J.Michaelson6 | Dorret I.Boomsma14 | Margaret J.Snowling19 |
CharlesHulme20 | Andrew J. O.Whitehouse21 | Craig E.Pennell3 | Dianne F.Newbury22 |
JohnStein23 | Joel B.Talcott24 | Dorothy V. M.Bishop19 | SilviaParacchini1
1School of Me dic ine, Un ivers ity of St Andrew s, St And rews , UK
2Depa rtment of Spe ech a nd Hear ing Scienc es, Un ivers ity of New Mexico, Albuqu erque, New Mexi co, USA
3School of Medic ine a nd Publ ic Hea lth, University of Newc astl e, Cal lagh an, New S outh Wales, Austr alia
4Depa rtment of Psyc hology, Uni versit y of York, York, UK
5Depa rtment of Edu cation, University of York, York, UK
6Depa rtment of Psyc hiatry, The University of Iowa, Iowa City, Iowa, USA
7Division of Experiment al and Translat ional Neuros cience, K rembil Research Institute, Un iversity Health Net work, Toronto, Ont ario, C anada
8Progr am in Ne uroscien ce and Me ntal He alth , Hospit al for Sick C hildren , Toronto, Ontar io, Canada
9Department of Physiology, Universit y of Toronto, Toronto, Ontar io, Canada
10Department of Paediatric s, Universit y of Toronto, Toronto, Ontario, Ca nada
11Dep art ment of Psycholog y, Hospita l for Sick Child ren, Toronto, O ntar io, Can ada
12Genetics a nd Genome Biology, Hospit al for Sick Children, Toronto, Ontario, Ca nada
13Dall a Lana S chool of P ubli c Healt h, Unive rsity of Toronto, Toronto, Ontar io, Can ada
14Dep art ment of Bio logic al Psychology, Vrije Univer site it Ams terdam, Amsterdam, The Net herla nds
15Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, Ludwig- Maximilians- University Hospital Munich, Munchen, Germany
16Julius- Maximilians- University Würzburg, Würzburg, Germany
17Language and Geneti cs Department , Max Pla nck Institut e for Psycholing uistics, N ijmege n, The Netherlands
18Donde rs Ins titut e for Brai n, Cog nition and Be haviou r, Radbou d Univer sity, Nijmegen, T he Neth erlan ds
19Depa rtm ent of Exp erimenta l Psychology, Unive rsit y of Oxford , Oxford, UK
20Departme nt of Education , Univer sity of O xford, O xford, UK
21Telethon Kids Institute, Univer sity of Wester n Austr alia , Pert h, Weste rn Aust ral ia, Austral ia
22Department of Biologica l and Medica l Sci ence s, Ox ford Brooke s University, Ox ford, UK
23Departme nt of Physio logy, Unive rsity of Oxford , Oxford, UK
24Aston Brain Ce nter, Sc hool of Li fe and Hea lth Sc ienc es, A ston Uni versit y, Birm ingham, UK
DOI: 10.1111/cdev.13914
This is an open acc ess artic le under the term s of the Creative Commons Attribution Li cense, wh ich pe rm its us e, distribution and reproduction in any mediu m,
provided the or iginal work is p roperly cite d.
© 2023 The Aut hors. Child Development published by Wil ey Periodicals LLC on beha lf of So ciet y for Rese arch i n Chi ld Developme nt.
Abbreviations: ALSPC, Avon Long itud inal Study of Pa rents and Ch ildr en; CCC, Childrens Com muni cation Chec kli st; DLD, developmental la nguage dis order;
GWAS, Genome- wide assoc iation stud ies; ICD, Int ern ationa l Classif ication of Dis eas e; KEMH, K ing Edward Memoria l Hospit al; LH, left- han ded; N RH,
non- rig ht- hande dne ss; NT R, Nethe rland s Twin Regi ster; QH P, Quantitative Han d Prefe renc e; RD, rea ding d isabilit y; RH, right- handed ness; SWRT, Single - Word
Readi ng Test; TOLD- 2P, Test of Langu age Developme nt 2:P; TROG– 2, Test for Re cept ion of Gr amm ar Versio n 2; WAIT, Wechsler Indivi dual Ac hieve ment Test
Spelling Test; WISC, Wech sler I ntelligen ce Sc ale for Ch ildren.
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LANGUAGE- RELATED IMPAIRMENTS AND HANDEDNESS
Handedness is the most obvious lateralized behavioral
trait in humans. Most individuals preferentially use
one hand versus the other one for most motor tasks,
with a strong rightward bias. Across populations, only
about 10% of people are left- handed (LH; Papadatou-
Pastou et al.,2020), with males being ~23% more likely
than females to prefer the left hand (Papadatou- Pastou
et al.,2008). Twin studies have estimated the heritability
of handedness to be 0.25 (Medland et al., 2009). Hand
activities are controlled by the contralateral brain hemi-
sphere such that a right- or left- hand preference implies
a left- or right- hemisphere dominance for motor control,
respectively (McManus,2022). The low frequency of left-
handedness across populations has motivated investiga-
tions of possible associated disadvantages. A higher rate
of non- right- handedness (NRH), which includes left- and
mixed- handedness, has been reported for neuropsychiat-
ric and neurodevelopmental conditions, such as schizo-
phrenia, autism, and intellectual disability (Hirnstein &
Hugd ahl, 2014; Markou et al., 2 017; Papadatou- Pastou
& Tomprou, 2 015). The underlying hypothesis is that
the genetic pathways required for establishing left– right
brain asymmetries might also contribute to handed-
ness and be involved in neurodevelopmental conditions
(Corballis, 2021). It is important to emphasize that the
majority of left- handers are not affected by these con-
ditions and therefore left- handedness should not be
equated to a pathological status.
A link between handedness and language abilities is
of particular interest because of the known role of hemi-
spheric lateralization under pinning both traits. Language
processing is highly lateralized, involving circuits that
reside typically in the left hemisphere, as demonstrated
by patients who had language function compromised as
the result of strokes affecting the left side of the brain
(Kertesz & McCabe,1977). Left- handers are more likely
than right- handers to present atypical lateralization for
language processing. Specifically, current estimates show
that up to 30% of left- handers present language dom-
inance in the right hemisphere compared with only 5%
of right- handers, with substantial variability across stud-
ies (Carey & Johnstone, 2014; Knecht, 2001; Szaf larski
et al., 2002; Whitehouse & Bishop, 2009; Woodhead
et al.,2 021). Such association is more evident in individ-
uals with a very strong left- hand preference (Mazoyer
et al.,2014). Sim ilarly, atypic al laterali zation for other cog-
nitive domains is more likely to be observed in left- than
right- handers (McManus,2022). Hemispheric dominance
for manual praxis (i.e., skilled manual actions) usually re-
sides in the left hemisphere but atypical lateralization has
been observed in left- handers (Vingerhoets, 2019). The
pathways involved in and linking different types of asym-
metries remain unclear (Fagard,2013).
The hypothesis that a failure to establish cerebral
asymmetries may lead to language disorders was first
proposed by Orton who suggested that dyslexia resulted
from a failure to establish a complete cerebral dominance
(Or ton, 1937). Subsequently, the Geschwind- Galaburda
Hypothesis (Galaburda et al., 1985) proposed that re-
duced hemispheric asymmetries increase the probabil-
ity of being LH and of developing dyslexia (Galaburda
et al.,1985). Annett's Right- Shift theory also predicted a
lin k between NRH and dyslexia determ ined by an “asym-
metry gene” which would affect the typical left hemi-
sphere lateralization for both language and handedness.
This, and other single- gene theories (McManus, 1985 )
are not supported by recent genomic studies which show
that in most cases, handedness is influenced by the
combined effects of variants in a large number of genes
(Armour et al.,2014; Cuellar- Partida et al.,2021; Schmitz
et al.,2022). Genome- wide association studies (GWAS)
for handedness have identified some of these genes,
some of which have also been implicated in neurodevel-
opmental conditions, including schizophrenia and dys-
lexia (Brandler et al.,2013; Brandler & Paracchini,2014;
Cuellar- Partida et al.,2021; Wiberg et al.,2019).
Correspondence
Silvia Para cch ini , School of Medicine ,
University of St A ndre ws, St An drews, UK.
Emai l: sp58@st-andrews.ac.uk
Funding information
Canadian I nstit ute for Health Res earch,
Grant /Award Number: MOP- 133440;
H2020 Eu ropea n Rese arch C ounc il,
Grant /Award Number: 694189; National
Health and Med ical Resea rch Cou ncil,
Grant /Award Number: 1173896, 572613,
403981 and 1059711; NWO, Grant /Award
Number : 451- 15- 017; Royal Society, Grant/
Award Numbe r: UF150663 and RGF\
EA\180141; Wellcome Trust , Grant/
Award Numbe r: 217065/Z/19/Z; University
of Bris tol; Hosp ital for Sick Ch ildr en
Resea rch Trai ning Progr am (Re stracomp);
Max Planck Soc iety; Deuts che
Forsc hung sge mei nsc haf t (DFG)
Abstract
Handedness has been studied for association with language- related disorders
because of its link with language hemispheric dominance. No clear pattern has
emerged, possibly because of small samples, publication bias, and heterogeneous
criteria across studies. Non- right- handedness (NRH) frequency was assessed in
N=2503 cases with reading and/or language impairment and N=4316 sex- matched
controls identified from 10 distinct cohorts (age range 6– 19 years old; European
ethnicity) using a priori set criteria. A meta- analysis (Ncases= 1994) showed
elevated NRH % in individuals with language/reading impairment compared with
controls (OR = 1.21, CI = 1.06 – 1.39, p= .01). The association between reading/
language impairments and NRH could result from shared pathways underlying
brain lateralization, handedness, and cognitive functions.
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ABBONDANZA et al.
Language- associated disorders, including dyslexia (or
reading disability, RD) and developmental language dis-
orders (DLD previously referred to as specific language
impairment) are reported in about 5%– 10% of children,
present higher prevalence in males and often co- occur
(Bishop & Snowling, 2004). In both conditions, genetic
contributions play a role, with strongest risk factor being
an affected first- degree family member (Arnett et al.,2017;
Erbeli et al.,2021; Katusic et al.,20 01; Tomblin et al.,1997;
Whitehouse,2010). In twin studies, heritability for both
RD and DLD has been reported to be as high as ~70%
(Erbeli et al., 2 021). Although rare monogenic forms of
reading and language disorders have been reported, the
majority of cases are polygenic with shared genetic fac-
tors contributing to both conditions, as shown by recent
and well powered GWASs (Eising et al., 2022; Gialluisi
et al.,2 014 , 2019, 2020). For example, the genetic correla-
tion between single- word reading (a task used to assess
reading abilities) and nonword repetition (a measure of
speech perception, phonological short- term memory and
articulation) was reported to be r= .7, p < .001 (Eising
et al., 2022). Genetic studies have also demonstrated
complex overlaps between genes contributing to neuro-
developmental disorders, handedness and left/right brain
asymmetries. The most recent GWAS for dyslexia con-
ducted in almost 52,000 cases and over 1 million controls
reported a signif icant genetic correlation between dyslexia
and ambidexterity (Doust et al.,2021). Genes associated
with handedness have been shown to be associated with
regional asymmetries of cortical surface areas, including
those involved in language- related circuitry (Sha, Pepe,
et al.,2021). A GWAS for brain asymmetry highlighted the
role of genes involved in autism and schizophrenia (Sha,
Schijven, et al.,2021). Overall, these findings demonstrate
with molecular data that brain asymmetries, handedness,
and neurodevelopmental disorders, including language-
related conditions, are partially influenced by the same
genes. Variants in these shared genes can increase the
chances of both being LH and having a neurodevelop-
mental disorder. The cellular functions associated with
the shared genes include cytoskeletal dynamics and the
left– right patterning of visceral organs (Paracchini,2021),
supporting the hypotheses that behavioral and anatomi-
cal asymmetries might, at least partly, be influenced by
the same factors (Brandler & Paracchini,2014).
At the behavioral level, putative links between handed-
ness and language conditions have been tested both across
the normal range of variation observed in the general
population as well as in cohorts clinically ascertained for
RD or DLD. The literature surrounding a link between
handedness and dyslexia is inconsistent, as determined
by meta- analyses (Bishop,1990; Eglinton & Annett,1994;
Somers et al., 2015). In 1990, Bishop conducted a meta-
analysis of 25 studies examining a total of N= 14,159
individuals (Bishop,199 0). Overall, a non- significant in-
crease of NRH was found in individuals with dyslexia.
However, the increase was statistically signif icant only
when the largest study, which had a negative finding and
weighted disproportionately on the overall analysis, was
omitted. When reanalyzing the complete dataset with a
different method, Eglinton and Annett reported a sig-
nificant over- representation of NRH among cases with
dyslexia (Eglinton & Annett,1994). In addition to the in-
consistency resulting from different analytical methods,
Bishop(1990) noted how the heterogeneous criteria used
for handedness and dyslexia classification introduced
biases in the analyses. For example, studies included in
the meta- analyses measured handedness either as quanti-
tative indexes (Annett & Kilshaw,1984) or as a category
(Felton et al.,1987; Gross et al., 1978). Also, individuals
were classified as reading impaired through highly hetero-
geneous criteria. A recent study compared the epidemiol-
ogy of dyslexia using both the Statistical Manual in its 5th
version (DSM- 5) and the 11th version of the International
Classification of Diseases (ICD- 11) on the same sample
of 25,000 French pupils. Left- handedness was associated
with dyslexia as defined by the DSM- 5 but not according
to the ICD- 11 criteria (Di Folco et al.,2022).
A meta- analysis for studies investigating potential
links between handedness and language abilities found
no significant effects in the entire dataset (N= 359,890
total individuals; Somers et al., 2 015). No differences
were detected between males and females. However,
analysis in the subgroup of children (age < 16 ye ar s)
showed a weak handedness effect with right- handers per-
forming better than non- right- handers on verbal skills.
High heterogeneity was reported across the studies an-
alyzed reflecting different criteria for group assignment.
For example, handedness was assessed in different ways
across studies, including self- reported hand preference
for writing (Crow et al.,1998; Gordon & Kravetz, 19 91;
Kocel,1977; Peters et al.,2006), different questionnaires
(Coulson & Lovett, 2004; Hicks & Beveridge, 1978;
Tremblay et al.,2004) and quantitative indexes derived
from performance tests like the pegboard task (Annett
& Turner, 1974). Inconsistent findings continue to be
observed in more recent literature. A small study of 45
individuals with dyslexia and 90 controls found a sig-
nificant increase of left- handedness, measured with the
Edinburgh Inventory, in the cases (Vlachos et al.,2013).
A right- hand advantage was also reported in a larger
study of about 5000 children from the Longitudinal
Study of Australian Children (Johnston et al.,2009). LH,
and especially mixed- handed children, tended to per-
form worse on a broad range of cognitive skills, including
reading, writing, and receptive language. This handed-
ness effect was more marked in boys. A similar trend was
observed for receptive language, but not for expressive
language, implying that NRH- associated effects might
differ between language sub- domains. Another study
with a focus on language abilities found no handedness
differences between typically developing (N= 156) and
children with DLD (N=107; Wilson & Bishop,2018). In
this study, handedness was measured with the Edinburgh
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LANGUAGE- RELATED IMPAIRMEN TS AND H ANDEDNES S
Handedness Inventory and the Quantitative Hand
Preference (QHP) tasks (see Bishop et al.,1996 ). The QHP
assessment did not show a correlation between handed-
ness and language scores in a general population sample
of 569 children (Pritchard et al.,2019).
The inconsistency across results conducted for both
reading and language impairment may be due to the
different criteria and designs used across studies. Meta-
analyses are a valid approach to extract the most consis-
tent patterns from published studies, although it must be
acknowledged that this approach is affected by potential
publications biases.
We invited cohorts from the GenLang consortium
(https://www.genla ng.org/) to participate in this confirma-
tory study. GenLang is an international collaboration that
facilitates large- scale meta- analyses in relation to speech,
language, reading and related skills. The association be-
tween hand preference and language/reading abilities has
not been i nvestigate d before in these c ohorts. T hanks to the
availability of raw data, we were able to apply criteria set
a priori for defining reading and language impairments to
reduce heterogeneity across cohorts. Handedness catego-
ries were defined as non- right (NRH) or right- handedness
(RH) based on the preferred hand for writing or drawing.
We report handedness frequency in 10 different cohorts
(N= 2503 cases with reading and/or language impair-
ment). Eight of these cohorts met the inclusion criteria and
entered the meta- analysis (N=1994 cases).
MATERIALS AND METHODS
Study design
This study aims to test whether hand preference is as-
sociated with language and reading abilities by com-
paring the frequency of RH and NRH in cases and
controls. We used datasets available through the
GenLang Consortium because of their focus on read-
ing and language measures (Ta ble1). Assignment to
case and control groups was based on an existing clini-
cal diagnosis or was derived from psychometric tests
(Tab l e S1). In the latter case, assignment to the case
group was determined by a score 1 SD or more below
the mean on standardized tests for assessing reading
or language performance. Participants presenting low
scores on performance IQ (i.e., 1SD below the mean,
unless otherwise specified) were excluded to ensure
that poor language/reading skills were not secondary
manifestations of other neurological or intellectual
problems. Children scoring poorly on both language
and reading measures were classified as comorbid.
Assignment to the control group was based on scores
equal to or above the mean of the same reading and
language tests, unless otherwise specified. As a result,
individuals that scored between the cut- off criteria for
cases and control assignment were excluded from the
analysis, ensuring that the controls had no reading or
language difficulties. The control groups were individ-
ually sex- matched with the cases to avoid potential bias
introduced by the higher prevalence of language dis-
order and left- handedness in males. Handedness was
defined as the preferred hand for writing and classified
as two categories: right- hand (RH) or non- right- hand
(NRH) preference. The NRH group included partici-
pants who preferred the left- hand or with no preference
(often referred to as ambidextrous). The ambidextrous
group was too small to be analyzed separately. This
strategy avoided the heterogeneity introduced by the
use of different instruments (e.g., different question-
naires or performance test) and classifications (e.g.,
left/right, right/no- right, left/mixed/right and left/
non- left) reported in the literature. Controls were
not available for three clinical cohorts (UK Dyslexia
TABLE 1 Summ ary of the cohorts involved in the study.
Cohort Country To t a l NaCohort type Phenotype References
AL SPAC c oho r t UK ~13,000 Epidemiological, singletons Reading, language Boyd et al.(2013)
Iowa Cohort USA ~7000 Epidemiological, singletons Language Tomblin et al.(1997 )
Netherlands Twin Reg ister cohort Netherlands ~60,000 Epidemiological, twins Reading Lig thart et al.(2019)
The Rai ne Study Austral ia ~2900 Epidemiological, singletons Language New nha m et al.(1993),
Straker et al.(2017 )
Twins Early Development Study
cohort
England and
Wal e s
~13,000 Epidemiological, twins Reading, language Haworth et al.(2 013)
Manchester Language Study UK ~240 Clinical, singletons Language Conti- Ramsden
et al.(1997 )
Multicenter Study Marbu rg/
Würzburg cohort
Germany ~400 Clinica l, singletons and
families
Reading Schulte - Körne
et al.(1996 )
Toronto Cohort Canada ~860 Clinical, families Reading Pr ice et al.(2020)
UK Dyslexia Cohort UK ~1300 Clin ical, sing letons and
families
Reading Sc erri et al.(2 017 )
York cohort UK ~260 Clinical, families Reading, language Nash et al.(2013)
aRefers to t he total numb er of probands i n the in itial cohort s.
974
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ABBONDANZA et al.
[UKDYS], Manchester Language Study (MLS) and the
Multicenter Study Marburg/Würzburg cohort). For the
two UK cohorts, controls were derived from the Avon
Longitudinal Study of Parents and Children (ALSPAC)
cohort which used directly comparable assessment.
The third cohort was collected in Ger many and could
not be matched with suitable controls. This cohort and
another (Netherlands Twin Register cohort [NTR]) did
not meet the required inclusions and exclusions criteria
and therefore were not included in the meta- analysis.
Nevertheless, their handedness frequencies are pre-
sented in Table2. We compared the mean values of
possible confounding factors (i.e. performance IQ, total
IQ, and birth weight) for the cases stratified by their
handedness status (TableS2). We observed no differ-
ences for these potential confounders between RH and
NRH cases and therefore did not correct our analyses
for such factors.
Overall, this study addresses a long- standing research
question addressing previous limitations, for example,
small samples, publication bias and heterogeneity, which
affected previous literature.
Given this is a secondary data analysis study,
full compliance to the Society for Research in Child
DevelopmentSociocultural Policy was not possible.
Individual cohorts
AL S PAC c ohor t
The ALSPAC is a longitudinal cohort representing
the general population living in the Bristol area. The
ALSPAC cohort consists of pregnant women in the Avon
County, UK, with expected dates of delivery from April
1, 1991 to December 31, 1992 (Boyd et al.,2013; Fraser
et al.,2013). The initial number of pregnancies enrolled
was 14,541. All children, from age 7, were invited annu-
ally for assessments on a wide range of physical, behav-
ioral, and neuropsychological traits, including cognitive
(reading - and language- related) measures. Attendance
at the annual assessment determined the availability of
data for the measures used in this study.
For this study, participants were assigned to the lan-
guage impairment or reading impairment groups as de-
scribed previously (Scerri et al., 2011). Briefly, children
were excluded if they had (i) a performance IQ score ≤ 85
(Wechsler Intelligence Scale for Children [WISC- III];
Wechsler et al., 1992), (ii) presence of autistic features
based on a Childrens Communication Checklist (CCC)
score below −3 SD (Bishop, 1998) (iii) missing data on
all relevant phenotypes. Participants were assigned to
TABLE 2 Non- right- handedness frequencies.
Cohort name Cohort type Phenotype
N cases N controls %NRH
NRH
(mal es)
RH
Males %
NRH RH
Malese%Cases Controls(mal es) (mal es) (males)
AL SPAC L ang ua ge Epidemiolog ical Language 27 (15 ) 214 (127) .59 112 (69) 749 (450) .60 .11 .13
AL SPAC R e a d i ng Epidemiological Readi ng 30 (22) 168 (101) .62 112 (69) 749 (450) .60 .15 .13
IOWA c ohor t Epidemiological Language 22 (16) 18 2 (10 5) .59 56 (35) 610 (360) .59 .11 .08
NTR cohortaEpidemiological Re ading 31 (18) 203 (97 ) .49 136 (66) 914 (450) .49 .13 .13
The Rai ne Study Epidem iological Language 21 (15) 136 (87) .65 49 (37) 389 (248) .65 .13 .11
TEDS Reading Epidemiological Readi ng 29 (8) 163 (84 ) .48 143 (60 ) 1031 (431) .42 .15 .13
TEDS Lang uage Epidemiological Language 3 4 (11) 187 (75 ) .39 143 (60 ) 1031 (431) .42 .15 .12
Manche ster Langu age
Studyb
Clinical Language 34 (28) 133 (103) .78 93 (69) 586 (450) .76 .20 .14
Multicenter Study
Marburg/Würzburgc
Clinical Reading 22 (19) 255 (189) .75 NA NA NA .08 NA
Toronto cohort Clinical Rea ding 28 (16) 207 (137 ) .65 7 (4) 50 (33) .65 .12 .12
UK DYSbClinical Reading 40 (24) 26 2 (181) .68 9 8 (69) 667 (45 0) .68 .13 .13
York Reading Clinical Read ing 11 (8 ) 25 (18) .72 13 (11) 57 (37) .69 .30 .18
York Language Clinical Language 9 (8) 30 (18) .67 13 (11) 57 (37 ) .69 .23 .18
Tot al 2503 4, 316 d
Note: The table in clude s the co morbid i ndiv idua ls in the lang uage i mpairme nt group.
Abbrev iation s: ALSPAC, Avon Longitudina l Study of Parent s and Ch ildren; NA, not ava ilab le; NRH, n on- rig ht- hand ers; RH, right- hande dne ss; TEDS , Twins
Early Developm ent Study; UKDYS, UK D yslex ia.
aThis c ohort wa s not include d in the m eta- a nalys is be caus e it lacked IQ data required for g roup assign ment. T he NRH f reque ncy is r epor ted .
bThese cohorts use d overlapping c ontrols from the A LSPAC cohort.
cThis cohort wa s not inc luded in the meta- analys is becaus e of the la ck of comparable controls.
dRefers to t he numb er of un ique c ontrols. Overl apping control s were a nalyzed for th e ALSPAC, Manche ster L angu age Study and the UKDYS cohorts.
eSex- matc hing for the ALSPAC, TEDS, and York cohort wa s done combining the r ead ing and language - impa ire d cases.
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LANGUAGE- RELATED IMPAIRMEN TS AND H ANDEDNES S
the reading impairment group when scoring below 1 SD
on age- adjusted single- word reading at age 7 and age 9
(WORD; Rust et al.,1993). Participants were assigned to
the language impairment group when meeting at least two
out of four of the following criteria: (i) an overall CCC
score below 1 SD from the mean; (ii) an age- adjusted
non- word repetition score below 1 SD from the mean
(Gathercole et al., 1994); (iii) a listening and comprehen-
sion test score below 1 SD from the mean (age- adjusted
WOLD; Rust,1996); (iv) reporting the need for speech/lan-
guage therapy via a questionnaire. In the case of siblings
and twin pairs meeting, the criteria for the impairment
group, one child for each nuclear family was selected ran-
domly or based on completeness of the data. Participants
were classified as comorbid when meeting the criteria for
both reading and language impairments. Assignment to
the control group was determined by scores above −0.25
SD from the mean on all the quantitative tests used to as-
sess language and reading impairments as well as no re-
ports of needs for speech/language therapy.
In total, 439 cases (191 language- impaired, 198 read-
ing impaired, 50 comorbid) and 1138 controls were iden-
tified. The control group resulted in 861 individuals after
sex- matching. The cut- off at −0.25 SD was chosen follow-
ing a simulation analysis (see Supplementary Material;
Tab l e S3) showing that N > 1000 controls are necessary
to reduce fluctuations in NRH frequency when ran-
domly sex- matching (Nsimulation=1000). Setting the cut-
off above the mean of all tests would have resulted in a
smaller sample (N=592), leading to larger fluctuations
of NRH. We also used a simulation to test for potential
biases introduced by the use of a single set of controls
for comparing both the reading and language impair-
ment groups. No inflation was detected (Supplementary
Methods). The same observation applies to the Twins
Early Development Study (TEDS) and York cohorts.
Handedness was assessed as the self- reported preferred
hand for writing at age 7 and coded as a binary variable
(“Right” or “Left”). The study website contains details
of all the data through a fully searchable data dictionary
(http://www.brist ol.ac.uk/alspa c/resea rcher s/our- data/).
Ethical approval for the study was obtained from the
ALSPAC Ethics and Law Committee and the local re-
search ethics committees (http://www.brist ol.ac.uk/alspa
c/resea rcher s/resea rch- ethic s/). Informed consent for the
use of data collected via questionnaires and clinics was ob-
tained from participants following the recommendations
of the ALSPAC Ethics and Law Committee at the time.
Iowa cohort
The Iowa cohort is a cross- sectional epidemiologi-
cal study of early language ability in 5- and 6- year- old
children (Tomblin et al.,1997). A total of 7218 children
were screened for language ability with a 40- item sub-
set of the Test of Language Development 2:P (TOLD- 2P;
Newcomer & Hammill, 1988). Inclusion criteria for en-
tering the study included being monolingual English
speakers without hearing loss. The 26.2% of children
who failed the test during the language ability screen-
ing were selected to compose approximately half of the
final cohort. The other half was randomly selected from
the children who passed the screening test. In total,
the cohort included 1929 children. A more comprehen-
sive battery of language assessments— consisting of the
five principal subtests of the TOLD- 2P, and a discourse
task with both narrative comprehension and production
components (Culatta et al.,1983)— was used to derive a
composite language score (age 5– 6). For this study, par-
ticipants were excluded if they had a performance IQ
score below 85 (WISC- IV; Wechsler,2012). Participants
scoring below 1 SD and above the mean on the compos-
ite score were assigned to the case and control group,
respectively. A total of 204 cases and 666 sex- matched
controls were selected. Handedness was defined as left-
or right- hand used to draw a picture, as assessed by the
ch i ld's ex am iner.
Analysis of the Iowa cohort was approved under the
University of Iowa IRB #201406727, which covers sec-
ondary data analysis of the data originally collected
under the University of Iowa IRB #200511767 under
which all subjects (or legal guardians) provided informed
consent/assent, as appropriate.
NTR cohort
The NTR is a national register including more than
120,000 twins and their relatives (Ligthart et al.,2019).
The twins were assessed repeatedly using a range of cog-
nitive and behavioral tasks at regular intervals. Teachers
provided test scores on the nationally standardized tests
that form the Dutch Pupil Monitoring System. Reading
ability (or decoding f luency) was assessed with a single-
word reading test by asking children to read aloud as
many words as possible from a word list within 1 min.
Children were tested at school in Grades 1– 6, with up
to three word- reading fluency lists, administered by
the teacher to children individually (Verhoeven, 1995;
Verhoeven & van Leeuwe,2009).
For the current study, the score at the latest measure-
ment was used. Children were excluded for (i) not at-
tending mainstream education programs, or (ii) missing
data. Participants were defined as cases if they scored
in the bottom 10th percentile based on the national
norms in Dutch education (equivalent to 1.28 SD below
the mean), which was the closest cut- off that could be
applied to conform to our criteria. Individuals scoring
above the mean of the national norms were assigned to
the control group. A total of 234 individuals with read-
ing impairment and 1050 sex- matched controls were se-
lected. Because of the lack of IQ data, this cohort was
not included in the meta- analyses.
976
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ABBONDANZA et al.
Handedness was recorded in questionnaires for the
mothers as hand preference for “drawing on a piece of
paper” at age 5. Answer options were right- , left- or no-
preference. The left- and no- preference were merged in
the NRH category.
Ethical approval was granted by the Vrije Universiteit
Amsterdam's Medical Ethics Committee (NTR/25-
05- 2007). Data were collected following parental consent.
The Raine Study
The Raine Study is a prospective pregnancy cohort
that recruited 2900 women between 1989 and 1991
(Newnham et al.,1993; Straker et al.,2017 ). Recruitment
took place at Western Australia's major perinatal center,
King Edward Memorial Hospital (KEMH), and nearby
private practices.
The mothers (Gen1) completed questionnaires re-
garding their children (Gen2) who underwent physi-
cal examinations at ages 1, 2, 3, 6, 8, 10, 14, 17, 20, and
22 years. The data used for this study were from the as-
sessment at 10 years of age. Participants were excluded
if they had a performance IQ score below 1 SD from the
mean assessed through the Raven Coloured Progressive
Matrices test (Raven et al.,1996). Total standard scores
of the CELF- 3 (Semel et al.,1995) were used for group as-
signments. Participants were assigned to the case group
when scoring equal or below 1 SD from the mean, and
to the control group when scoring above the mean. This
resulted in N=157 language- impaired cases and N=438
sex- matched controls. Hand preference for writing was
self- reported and recorded in the McCarron Assessment
of Neuromuscular Development (McCarron,1997).
The study was approved by the Human Ethics
Committee at KEMH, Princess Margaret Hospital for
Children, the University of Western Australia and the
Health Department of Western Australia.
TEDS cohort
The TEDS is a longitudinal study of a cohort of twins
from over 13,000 families born in England and Wales
between 1994 and 1996 (Haworth et al., 2013; Rimfeld
et al.,2019). The cohort includes a broad range of phe-
notypic data, including language and reading skills and
handedness. The TEDS website includes a complete data
dictionary https://www.teds.ac.uk/datad ictio nary/home.
html, which details exclusions based on medical and per-
inatal factors, missing data, and other factors. For this
study, participants were excluded if they had a perfor-
mance IQ score that was below 1 SD based on Raven
Matrices and Picture Completion tests. Individuals
were assigned to the language impairment group when
scoring 1 SD below a language composite score mean
(Hayiou- Thomas et al., 2021). Brief ly, the composite
score was based on a battery of audio- streamed, web-
administered measures including vocabulary (WISC-
III- PI; Kaplan, 1999), syntax (Listening Grammar;
Test of Adolescent & Adult Language- 3; Hammill
et al.,1994), non- literal semantics, and understanding of
inferences (Test of Language Competence- Level 2; Wiig
& Secord,1985) administered at age 12. Previous analy-
sis showed substantial phenotypic and genetic overlap
among these four measures (Dale et al.,2010). The four
tests were standardized and averaged.
Participants were assigned to the reading impairment
group if they scored 1 SD below the mean of a reading
fluency composite score (Hayiou- Thomas et al., 2021).
Brief ly, children completed an online adaptation of the
Woodcock- Johnson III Reading Fluency test (Woodcock
et al., 2001). In addition, the Test of Word Reading
Efficiency (TOWRE Form B; Torgesen et al.,1999) was
included in a test booklet sent to families by mail and ad-
ministered to each twin separately by telephone. Previous
work with the TEDS sample established strong concurrent
validity for telephone ad ministration of the TOWRE (Dale
et al.,2005). The tests were standardized and averaged.
Participants scoring 1 SD below the mean for both the
language and reading composite scores were assigned to
the comorbid group. Participants scoring above −0.25 SD
from the mean of both composite tests were assigned to
the control group. One child per twin pair was selected
at random if both twins had the relevant phenotypes. A
total of 413 cases (N=192 cases with reading impairment;
N=152 cases with language impairment, N=69 comor-
bid) and 1174 sex- matched controls were identified.
The primary measure of handedness was self- reported
at 16 years. It included a question asking the preferred
hand used for writing (left, right, mixed). The TEDS
study received ethical approval from the King's College
London Ethics Committee.
Manchester Language Study cohort
The MLS followed 242 children with language impair-
ment (Conti- Ramsden et al., 1997). Probands were re-
cruited at age 7 from 118 language units attached to
English mainstream schools (Conti- Ramsden et al.,1997;
Conti- Ramsden & Botting, 1999). Participants were
contacted and reassessed again at ages 8 (N= 232), 11
(N=200), 14 (N=113), 16 (N=139), and 24 (N=84) years
old. All children attended a language unit for at least 50%
of the week, and as such, met the criteria for a language
impairment diagnosis. Children with other neurological
difficulties, hearing impairment, a diagnosis of autism or
a general learning disability were excluded. Participants
were excluded when they had a Raven matrices perfor-
mance score IQ that was more than 1 SD below the mean.
A total of 167 cases were selected for the current study.
Handedness was assessed at age 8 as self- reported hand
preference (“are you left- or right- handed?”). If data
|
977
LANGUAGE- RELATED IMPAIRMEN TS AND H ANDEDNES S
were not available at age 8 (N=26), reports from age 14
were used. Hand preference was consistent in 97% of the
participants who had data at both time points. Controls
were not available for the MLS cohort, and therefore
were derived from the ALSPAC control group resulting
in N=679 after sex- matching.
Ethical approval was given by The University of
Manchester Research Ethics Committee, UK. Parents
or legal guardians provided informed consent for all par-
ticipants up to the age of 16 years.
Multicenter study Marburg/Würzburg cohort
The Marburg/Würzburg cohort is a family- based co-
hort that focuses on the genetic basis of reading im-
pairment (Schulte- Körne et al.,1996). Participants were
excluded if they had (i) Nonverbal IQ < 85 (Cult u re Fa ir
Intelligence Test; Weiß,1998), (ii) presence of visual or
auditory impairments, (iii) inadequate schooling and
absences for more than 6 weeks per school year, (iv) first
language other than German, (v) diagnosis of attention
deficit hyperactivity disorder (ADHD), and (vi) pres-
ence of psychiatric disorders, seizure disorder, and use
of medication affecting the central nervous system. The
study enrolled 403 probands between 8 and 19 years old
(grades 2 to 11). Probands were assessed on a large cog-
nitive battery including reading and arithmetic skills,
and neurophysiological correlates (ERP studies) associ-
ated with language and reading processing. Of the 403
participants, 277 scored more than 1 SD below the mean
on single- word reading (see Schulte- Körne et al.,1996)
meeting the criteria for assignment to the reading
impairment group. Handedness was measured by a
questionnaire including 10 items describing a specif ic
activity (e.g., writing, throwing a ball, brushing teeth).
Participants reported which hand they used for the spe-
cific activity based on a four- point rating scale (1=al-
ways left, 2 = mostly left, 3 =mostly right, 4 = always
right). For the current study, only hand preference for
writing was considered. Answers 1 and 2 were coded as
“non- right” and answers 3 and 4 were coded as “right.”
No controls assessed with comparable measures were
available, and therefore, this cohort was not included in
the meta- analyses. Ethical approval was obtained from
the ethics committees of the Universities of Marburg
and Würzburg.
Toronto cohort
Children between the ages of 6 and 16 years who strug-
gled primarily with reading acquisition were recruited
from the Toronto area and across Ontario (Couto
et al., 2008; Elbert et al., 2011; Price et al., 2020; Tran
et al.,2014). Siblings in the same age range with or with-
out reading difficulties were also invited to participate.
Individuals were excluded for a performance
IQ < 80 (WISC- III) on either Verbal Comprehension
or Perceptual Reasoning on the WISC- IV. Three main
reading subtests were used to determine reading im-
pairment: (i) Word Identification and (ii) Word Attack
from the Woodcock Reading Mastery Tests Revised
(Woodcock,1987) and (iii) Reading subtest of the Wide
Range Achievement Test (WRAT- 3; Wilkinson, 1993)
Individuals were assigned to the reading impairment
group if they scored at least 1.5 SD below the mean on
2 out of 3 reading measures or at least 1 SD below the
mean on all three measures. Controls were defined as
scoring above the mean on all three measures. A total of
235 cases and 57 sex- matched controls were included in
the analyses. If families included multiple children meet-
ing these criteria, one child was selected at random.
Right- and left- hand preference was determined
by a psychometrist as the child wrote to complete the
WISC- IV Coding test. The participants provided ver-
bal or written consent and the parents provided written
consent. The study was approved by the Hospital for
Sick Children and University Health Network Research
Ethics Boards.
UKDYS cohor t
The UKDYS cohort includes nuclear families and sin-
gletons recruited to study the genetics of dyslexia (Scerri
et al., 2 010, 2017 ). The family cohort was recruited by
research clinics in Oxford and Reading and included 689
siblings from 409 families. The singleton cohort was re-
cruited in clinics in Oxford, Reading and Aston, and in-
cluded 676 children. The age at assessment ranged from
7 years to 18 years.
For this study, individuals were excluded when pre-
senting performance IQ scores <85 (WISC- III) and were
assigned to the case group if they scored at least 1 SD
below the mean on the British Abilities Scales single- word
reading test (Thomson, 1982). Handedness was defined
as self- reported hand preference for writing (“Right” or
“Left”). In total, 302 children met the criteria for read-
ing impairment. Controls were derived from the main
ALSPAC control group (N=765 sex- matched controls).
Ethical approvals for the Oxford family and case/con-
trol cohorts were granted by the Oxfordshire Psychiatric
Research Ethics Committee (OPREC O01.02). Ethical
approval for the Aston cohort was granted by the Aston
University Ethics Committee.
York cohort
The York cohort compris es 260 childr en who were followed
longitud inally in a study of l anguage and rea ding disorders
(Nash et al., 2013). Children were assessed on a battery
of cognitive, language, and reading tests approximately
978
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ABBONDANZA et al.
annually between the ages of 3½ and 9 years. Assignment
to the reading and language impairment group was based
on the assessment at age 8– 9 years old (described fully in
Snowling et al.,2019). Children with performance IQ < 85
(WISC- IV) were excluded. For this study, a reading im-
pairment outcome was defined based on a score 1 SD or
more below the mean, on a reading composite measure of
the Single- Word Reading Test (SWRT 6– 16; Foster,2007)
and the Wechsler Individual Achievement Test Spelling
Test (WIAT– II; Wechsler, 2005). A language impair-
ment outcome was defined based on a score 1 SD or more
below the mean, on a composite language measure of
Expressive Vocabulary (CELF– 4 UK; Wiig et al.,2006),
Test for Reception of Grammar Version 2 (TROG– 2;
Bishop, 2003), and Formulated Sentences (CELF– 4).
According to these criteria, 36 children had reading im-
pairment, 20 children had language impairment, and
19 children showed comorbidity for both conditions.
Participants scoring above the mean for both the reading
and language composite scores were sex- matched to the
combined cases, resulting in N=70 controls. Handedness
was defined as self- reported hand preference for writing
collected at age 8 years as “Right” or “Left” categories.
Ethical approval for the study was provided by the
University of York, Department of Psychology's Ethics
Committee and the NHS Research Ethics Committee.
Parents provided written informed consent for their
child to be involved.
Statistical analyses
Handedness frequency was compared between cases
and controls using random- effect meta- analyses with
and without moderators for impairment type (lan-
guage/reading impairment) and cohort type (clinical/
epidemiological). The number of individuals with co-
morbidities was too small to be analyzed separately and
was therefore combined with the language impairment
group. The analysis was also run including individuals
with comorbidities in the reading impairment group (see
Supplementary Material).
Meta- analyses were conducted using the rma func-
tion in the R package metafor (t e st =“knha,” Balduzzi
et al.,2019; R Core Team,2019) under REML random ef-
fect model. T he presence of het erogeneity between groups
was explored using the Cochran's Q test and the I2 index.
The summary data for all cohorts and the code to run the
analysis are available at http s://git hub.com /fabbondanza/
GenLang_hand_preference_meta_analysis.
RESULTS
We investigated the frequency of NRH in individu-
als with reading or language impairment (N total
cases=2503) from 10 cohorts (Table2). Overall, the NRH
frequency ranged from 8% in the Multicenter Study
Marburg/Würzburg cohort (Ncases=277) to 30% in the
York reading cohort (Ncases=36). In the controls, NRH
ranged from 8% (IOWA, Ncontrol s= 666) to 18% (York,
Ncontrols=70). When excluding the York cohort, which
appeared to be an outlier for both cases and controls
and had a small sample size, the NRH frequency ranged
from 8%– 20% in the cases and 8%– 14% in the controls.
Meta- analysis
The NTR cohort and the Multicenter Study Marburg/
Würzburg cohort were excluded from the meta- analysis
because of the lack of IQ data or suitable controls, re-
spectively. We meta- analyzed data from 8 cohorts, in-
cluding 4 clinical and 4 epidemiological cohorts.
We observed an increase of NRH in the case group
(OR =1.21, C I = 1.06 – 1.39, t= 3.16, p= .01; Figure1).
Egger's t test showed no evidence of funnel plot asym-
metry (t=0.563, p= .59, df=9). We observed no evi-
dence of heterogeneity (Q (10) = 6 . 27, p= .79, τ2= .01,
I2=0%; see FigureS1 for funnel plot). When the MLS
and UKDys which lacked independent controls were
removed, the results remained comparable to those ob-
served in the full datasets (OR= 1.19, CI = 1.03– 1.38,
t=2.78 , p=.02, FigureS2). Inclusion of the comorbid
individuals as part of the reading impairment group
made no major difference (FiguresS3 and S4). The
lowest OR (0.84) was observed for an epidemiological
cohort, while the highest ORs (1.93) were observed in
clinical cohorts. However, a formal analysis did not re-
veal a moderator effect of cohort type (clinical vs. ep-
idemiological; p=.21) or type of impairment (reading
vs. language; p=.59).
DISCUSSION
We investigated the prevalence of NRH in individuals
with reading and language impairments in a total of
2503 cases from 10 cohorts. NRH frequency tended to
be elevated and presented a wider range of variation in
the cases (8%– 30%) compared with the controls (8%–
18%). The upper range of variation was observed in the
York cohort for both cases and controls, possibly sug-
gesting a bias introduced by how NRH was assessed.
However, the NRH prevalence in this cohort could have
also been inflated random variations associated with
the small sample size and the high rate of males. The
second- highest level of NRH was observed in the MLS
(20%), a clinical cohort collected for language impair-
ment. The high rate of NRH likely reflects a genuine
association with a particularly severe language pheno-
type considering that the MLS was recruited follow-
ing very stringent inclusion criteria. The lowest level
of NRH in cases (8%) was observed in the Multicenter
|
979
LANGUAGE- RELATED IMPAIRMEN TS AND H ANDEDNES S
Study Marburg/Würzburg cohorts which lacked inter-
nal controls and therefore could not be evaluated for a
potential assessment bias.
The meta- analysis was conducted in the eight cohorts
that met the inclusion criteria (Ncases= 1994). Overall,
we observed a higher rate of NRH in individuals with
language/reading impairment compared with controls
(OR = 1.21, CI = 1.06 – 1.39, t= 3.16, p= .01). The avail-
ability of raw data allowed us to apply similar criteria for
group definition, yet it is worth noting that all cohorts an-
alyzed here were originally recruited for different types
of studies and designs. Nevertheless, no moderator ef-
fects were detected for impairment (reading vs. language)
or cohort type (epidemiological vs. clinical). No changes
in the results were observed when the comorbid groups,
which were too small to be analyzed individually, were
included in either the language or the reading impaired
groups. A similar but attenuated trend was observed after
removing the UKDYS and Manchester Language co-
horts, thus ruling out a possible bias introduced by the
lack of independent controls. The removal of the York
cohort, which represented an outlier, also led to a similar
but attenuated trend (OR= 1.19, CI = 1.03– 1.38, p=.02;
FigureS5). Although we analyzed almost 2000 cases, the
sample sizes of the individual cohorts were too small to
test subgroups selected for phenotype severity or disor-
der subtype, when considering the small effect size ob-
served in the whole sample. A systematic assessment of
handedness in larger cohorts of individuals, recruited and
assessed with the same criteria for reading or language
impairment, will be necessary to differentiate potential
group- specific effects and to evaluate differences between
clinical and population- based cohorts.
We acknowledge that the use of overlapping con-
trols derived from the ALSPAC cohort and used for the
UKDYS and Manchester Language cohort is not ideal,
as non- independent datasets might lead to biases (Noble
et al., 2 017 ). When the UKDYS and the Manchester
Language cohorts were excluded, the results were compa-
rable (same direction, but attenuated strength; OR=1.19,
CI= 1.03 – 1.38, p=.02) to the full dataset. An alterna-
tive option could have been the use of non- overlapping
controls from ALSPAC. However, a simulation analysis
showed that the use of smaller subsets of independent
controls would increase the f luctuation of NRH and
thus increase the noise in the analysis. Cultural factors,
such as stigma against left- handedness, are known to
vary to some extent with ethnicity and generations, but
this is not a concern for our study. The children analyzed
have similar birth years and large studies in the UK
Biobank have not identified geographical factors that
inf luence handedness prevalence within England (de
Kovel et al.,2019). However, it is worth noting that our
study is limited to cohorts of White European ancestry
and therefore generalizability of our results will require
analysis in other populations.
Previous meta- analyses of the literature have been in-
conclusive (Bishop,1990; Eglinton & Annett,1994; Somers
et al.,2015) and studies that applied different definitions of
dyslexia found inconsistent results in the same dataset (Di
Folco et al., 2022). When applying the DSM- 5, which is
more closely in line w ith the criteria adopted here, Di Folco
FIGUR E 1 Meta- analysis of non- right- handedness (NRH) frequency i n individuals with lang uage/reading i mpai rments. The forest plot
shows the re sults of the meta- analysis run under a random effe ct (RE) model. The OR esti mate s are shown with the 95% confidence i nter val
and the weights (i n percentages) on the overall resu lt of OR=1.21, CI=1.06 – 1.39 (t=3.16, p=.01). See FigureS1 for the c orre sponding funnel
plot. ALSPAC, Avon Longitudi nal Study of Parents and Children; RH, right- handed ness; TEDS, Twins Early Development Study; UK DYS,
UK Dyslexia.
980
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ABBONDANZA et al.
and colleagues found an association between handedness
and dyslexia that was very similar to our study (OR=1.24,
p=.003). The effect disappeared when applying the ICD-
11 definition which is based on IQ discrepancy. Di Folco
and colleagues concluded that the original effect was not
specific to reading but mediated by IQ. Such a conclusion
was supported by the observation that “non- right- handers
scored on average 2 IQ points lower than right- handers.”
When comparing IQ between NRH and RH cases in the
present study, we observed no significant differences with
the exception of the UKDYS cohort (uncorrected p=.03).
Our observation is in line with meta- analyses investigating
the associations between handedness and cognitive abili-
ties, which reported that right- handers had only margin-
ally higher scores compared with left- handers (Ntolka &
Papadatou- Pastou,2 017).
Some potential issues affecting the reliability of our
data could have been introduced by the assessment of
handedness at a young age. Hand preference can fluc-
tuate in the early years of development but is well es-
tablished by the time a child is 3 years old (McManus
et al.,1988). In all our cohorts, handedness data were col-
lected when children were at least 5 years old, and there-
fore after the handedness direction is fully established, as
demonstrated also by the high correlation of assessments
conducted at different time points (e.g., ALSPAC: r=.95
CI=[0.93, 0.97], p < 2.2 × 10−16 , Schmitz et al.,2022).
In summary, our study investigates an old question
with new data addressing issues that affected the previ-
ous literature, including small samples, heterogeneous
criteria, and publication bias. The findings support an
association, albeit small in size, between NRH and lan-
guage/reading impairment, expanding the range of neu-
rodevelopmental traits (e.g., autism and schizophrenia)
known to be associated with handedness. From these
data, it is not possible to infer any cause/effect direction-
ality between brain asymmetries, disorders, and handed-
ness but provide an important foundation for theoretical
framework. Our results are in line with the evidence
emerging from genetic studies supporting the role of
shared genes and biological pathways contributing to
both lateralization and neurodevelopmental disorders.
ACKNOWLEDGMENTS
The authors are grateful to all participants taking part in
the different studies and the research teams involved in
collecting the data. Specifically, we thank all the families
who took part in this study, the midwives for their help
in recruiting them, and the whole ALSPAC team, which
includes interviewers, computer and laboratory techni-
cians, clerical workers, research scientists, volunteers,
managers, receptionists and nurses; the Raine Study par-
ticipants and thei r families for their ongoing participation
in the study and the Raine Study staff for their dedicated
commitment to coordination and data collection. We
gratefully acknowledge the ongoing contribution of the
participants in the NTR, including twins, their families
and teachers. The authors are grateful to the Raine Study
participants and their families, and to the Raine Study
team for cohort coordination and data collection. The
authors gratefully acknowledge the NHMRC for their
long- term funding to the study over the last 30 years and
also the following institutes for providing funding for
Core Management of the Raine Study: The University
of Western Australia (UWA), Curtin University, Women
and Infants Research Foundation, Telethon Kids
Institute, Edith Cowan University, Murdoch University,
The University of Notre Dame Australia and The Raine
Medical Research Foundation. This work was supported
by resources provided by the Pawsey Supercomputing
Center with funding from the Australian Government
and the Government of Western Australia.
FUNDING INFORMATION
Silvia Paracchini and Filippo Abbondanza are funded
by the Royal Society (UF150663; RGF\EA\180141). The
UK Medical Research Council and Wellcome (Grant
ref: 217065/Z/19/Z) and the University of Bristol provide
core support for ALSPAC. This publication is the work
of the authors and will serve as guarantors for the con-
tents of this paper. A comprehensive list of grants fund-
ing is available on the ALSPAC website: http://www.brist
ol.ac.uk/alspa c/exter nal/docum ents/grant - ackno wledg
ements.pdf. The funders had no role in study design, data
collection and analysis, decision to publish, or prepara-
tion of the manuscript. Elsje van Bergen was supported
by NWO VENI fellowship 451- 15- 017. Support for the
Toronto c ohort collec tion was provided by g rants from the
Canadian Institutes of Health Research (MOP- 133440).
K.M.P. was supported by the Hospital for Sick Children
Research Training Program (Restracomp). Simon Fisher
is funded by the Max Planck Society. Dorothy Bishop
is funded by European Research Council Advanced
Grant 694189. Andrew Whitehouse is supported by
an Investigator Grant from the National Health and
Medical Research Council (1173896). The Raine Study
was supported by the National Health and Medical
Research Council of Australia (grant numbers 572613,
403981, 1059711), and the Canadian Institutes of Health
Research (grant number MOP- 82893). The Multicenter
Study Marburg/Würzburg cohort was funded by the
Deutsche Forschungsgemeinschaft (DFG).
ORCI D
Filippo Abbondanza https://orcid.
org/0000-0002-1799-5492
Philip S. Dale https://orcid.org/0000-0002-7697-8510
Uma r Tos e e b https://orcid.org/0000-0002-7536-2722
Elsje van Bergen https://orcid.org/0000-0002-5860-5745
Margaret J. Snowling https://orc id.
org/0000-0003-0836-3861
Charles Hulme https://orcid.org/0000-0001-7417-8926
Silvia Paracchini https://orcid.
org/0000-0001-9934-8602
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How to cite this article: Abbondanza, F., Dale, P S.,
Wang, C A., Hayiou- Thomas, M E., Toseeb, U.,
Koomar, T S., Wigg, K G., Feng, Y., Price, K M.,
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S. (2023). Language and reading impairments are
associated with increased prevalence of non- right-
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