Advanced parental age at birth is associated with poorer social functioning in adolescent males: shedding light on a core symptom of schizophrenia and autism.
ABSTRACT Evidence indicates an association between older parents at birth and increased risk for schizophrenia and autism. Patients with schizophrenia and autism and their first-degree relatives have impaired social functioning; hence, impaired social functioning is probably an intermediate phenotype of the illness. This study tested the hypothesis that advanced father's age at birth would be associated with poorer social functioning in the general population. To test this hypothesis, we examined the association between parental age at birth and the social functioning of their adolescent male offspring in a population-based study.
Subjects were 403486, 16- to 17-year-old Israeli-born male adolescents assessed by the Israeli Draft Board. The effect of parental age on social functioning was assessed in analyses controlling for cognitive functioning, the other parent's age, parental socioeconomic status, birth order, and year of draft board assessment.
Compared with offspring of parents aged 25-29 years, the prevalence of poor social functioning was increased both in offspring of fathers younger than 20 years (odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.08-1.49) and in offspring of fathers 45 years old (OR = 1.52, 95% CI = 1.43-1.61). Male adolescent children of mothers aged 40 years and above were 1.15 (95% CI = 1.07-1.24) times more likely to have poor social functioning.
These modest associations between parental age and poor social functioning in the general population parallel the associations between parental age and risk for schizophrenia and autism and suggest that the risk pathways between advanced parental age and schizophrenia and autism might, at least partially, include mildly deleterious effects on social functioning.
- [show abstract] [hide abstract]
ABSTRACT: To investigate perinatal risk factors for childhood Type 1 diabetes in a UK population cohort. Perinatal data have been routinely recorded in Northern Ireland for all births in the period 1971-86 (n = 447 663). Diabetes status at the age of 15 years was ascertained in this cohort by identifying 991 children from 1079 registered with Type 1 diabetes diagnosed from 1971 to 2001 and date of birth in the period 1971-86. Increased Type 1 diabetes risk was associated with higher maternal age, paternal age, birth weight and birth weight for gestational and lower gestational age. After adjustment for maternal age, the association between Type 1 diabetes and paternal age remained significant [relative risk (RR) = 1.52 (1.10, 2.09) comparing father's age 35 years or more to less than 25 years] but not vice versa [RR = 1.11 (0.80, 1.54) comparing mother's age 35 years or more to less than 25 years]. Increased birth order was associated with a significant decrease in the risk of Type 1 diabetes [adjusted RR = 0.75 (0.62, 0.90) comparing birth order three or more with firstborn], but this only became apparent when adjustment was made for maternal age. Furthermore this association with birth order was significant only for diabetes diagnosed under the age of 5 years. Our analysis demonstrates, for the first time in a UK regional cohort setting, that maternal age and paternal age at delivery, birth order, birth weight and gestational age are significantly associated with Type 1 diabetes risk.Diabetic Medicine 03/2005; 22(2):200-6. · 3.24 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Autistic disorder (MIM 209850) is currently viewed as a neurodevelopmental disease. Reelin plays a pivotal role in the development of laminar structures including the cerebral cortex, hippocampus, cerebellum and of several brainstem nuclei. Neuroanatomical evidence is consistent with Reelin involvement in autistic disorder. In this study, we describe several polymorphisms identified using RNA-SSCP and DNA sequencing. Association and linkage were assessed comparing 95 Italian patients to 186 ethnically-matched controls, and using the transmission/disequilibrium test and haplotype-based haplotype relative risk in 172 complete trios from 165 families collected in Italy and in the USA. Both case-control and family-based analyses yield a significant association between autistic disorder and a polymorphic GGC repeat located immediately 5' of the reelin gene (RELN) ATG initiator codon, as well as with specific haplotypes formed by this polymorphism with two single-base substitutions located in a splice junction in exon 6 and within exon 50. Triplet repeats located in 5' untranslated regions (5'UTRs) are indicative of strong transcriptional regulation. Our findings suggest that longer triplet repeats in the 5'UTR of the RELN gene confer vulnerability to autistic disorder.Molecular Psychiatry 04/2001; 6(2):150-9. · 14.90 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Previously reported associations between advancing paternal age and schizophrenia could be due to an increase in paternal germ cell mutations or be confounded by heritable personality traits associated with schizophrenia that result in delayed parenthood. To investigate this association while adjusting for personality traits related to poor social integration in the subjects. A cohort of 50,087 adolescent males was followed up by record linkage to determine hospital admissions for schizophrenia between 1970 and 1996. Advancing paternal age was associated with an increased risk of developing schizophrenia in a 'dose-dependent' manner. The adjusted odds ratio for each 10-year increase in paternal age was 1.3 (95% CI 1.0-1.5; P=0.015). Advancing paternal age is an independent risk factor for schizophrenia. Adjusting for social integration in subjects made little difference to this association, consistent with the hypothesis that advancing paternal age may increase liability to schizophrenia owing to accumulating germ cell mutations.The British Journal of Psychiatry 12/2003; 183:405-8. · 6.61 Impact Factor
Advanced Parental Age at Birth Is Associated With Poorer Social Functioning in
Adolescent Males: Shedding Light on a Core Symptom of Schizophrenia and Autism
Mark Weiser1–4, Abraham Reichenberg5,
Nomi Werbeloff2, Karine Kleinhaus6, Gad Lubin3,
Moti Shmushkevitch3, Asaf Caspi2,4, Dolores Malaspina7,
and Michael Davidson2,4
2Department of Psychiatry, Sheba MedicalCenter, Tel-Hashomer,
Ramat Gan 52621, Israel;3IDF, Division of Mental Health, Israel;
4Sackler School of Medicine, Tel Aviv University, Ramat Aviv,
Israel;5Institute of Psychiatry, London, UK;6Department of
Psychiatry, Colombia University, NY;7Department of Psychiatry,
New York University, NY
Background: Evidence indicates an association between
older parents at birth and increased risk for schizophrenia
and autism. Patients with schizophrenia and autism and
hence, impaired social functioning is probably an interme-
diate phenotype of the illness. This study tested the hypoth-
esis that advanced father’s age at birth would be associated
with poorer social functioning in the general population. To
test this hypothesis, we examined the association between
parental age at birth and the social functioning of their
adolescent male offspring in a population-based study.
Methods: Subjects were 403 486, 16- to 17-year-old
Israeli-born male adolescents assessed by the Israeli Draft
Board. The effect of parental age on social functioning was
assessed in analyses controlling for cognitive functioning,
the other parent’s age, parental socioeconomic status, birth
order, and year of draft board assessment. Results: Com-
pared with offspring of parents aged 25–29 years, the prev-
alence of poor social functioning was increased both in
offspring of fathers younger than 20 years (odds ratio [OR]
1.27, 95% confidence interval [CI]
offspring of fathers 45 years old (OR 1.52, 95% CI
1.43–1.61). Male adolescent children of mothers aged
40 years and above were 1.15 (95% CI 1.07–1.24) times
more likely to have poor social functioning. Conclusions:
These modest associations between parental age and
poor social functioning in the general population parallel
the associations between parental age and risk for schizo-
phrenia and autism and suggest that the risk pathways be-
tween advanced parental age and schizophrenia and autism
1.08–1.49) and in
might, at least partially, include mildly deleterious effects
on social functioning.
Key words: schizophrenia/social functioning/parental age
Advanced father’s age at birth has been associated with
increased risk of schizophrenia1–7and autism.8–10Ad-
vanced mother’s age at birth has also been associated
with schizophrenia5,11and autism,10but the evidence is
less consistent. It is hypothesized that schizophrenia
and autism are diseases affected by multiple genes and
environmental factors,12but these factors can also con-
tribute to the manifestation of other mental disorders or
intermediate phenotypes such as poor cognitive or social
functioning. It is further hypothesized that the deleteri-
ous effects of the risk factors are manifested as mental
illness only when individuals cross a certain severity
threshold.13Hence, advanced parental age might not
be a risk factor for a specific mental disorder such as
schizophrenia or autism but rather increases risk for
brain malfunction that rarely crosses the threshold for
a clinical diagnosis. Certain degrees of social impairment
are not uncommon in mental illness in general, and are
essential for the diagnosis of schizophrenia and autism.14
The present study therefore aimed to examine the hy-
pothesis that advanced parental age at birth is associated
with decreased social abilities, reflected by decreased so-
cial functioning, across the entire range of social func-
tioning levels in the general population. To this end,
we analyzed data on parental age and social functioning
from the assessments performed by the Israeli military on
all adolescent males in the country.
The Israeli Draft Board Registry includes cognitive and
behavioraldataonall16- to17-year-old Israeli males. The
draft board assessment includes a semistructured inter-
view assessing demographics (including parental age at
birth), personality, and behavioral traits, including social
functioning. College-aged individuals have to complete 4
1To whom correspondence should be addressed; tel: þ972-52-
666-6575, fax: þ972-3-6358599, e-mail: firstname.lastname@example.org.
? The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
For permissions, please email: email@example.com.
Schizophrenia Bulletin vol. 34 no. 6 pp. 1042–1046, 2008
Advance Access publication on September 15, 2008
months of training to qualify to administer the semistruc-
tured interview. The interview scale includes questions
such as How many good friends do you have? Do you
have a girl friend? Do you generally prefer to be with
or without a group of companions? How often do you
go out on Friday evenings? Do you tend to be the center
of the party? Scale points are (1) very poor—complete
withdrawal, (2) poor—weak interpersonal contacts, (3)
adequate—can form relationship with individuals and
in a group, (4) good—good interpersonal relationships,
and (5) exceptional—superior interpersonal relatedness.
The test-retest reliability of the behavioral assessment
for inductees interviewed after several days by different
interviewers is above 0.8, and population-based norms
are available for each of the tests.15,16
For purposes of this study, the total score of social
functioningwas used.Themedianforthe socialfunction-
ing score is 3, the mean score is 3.04, with an SD of 0.72,
and 25.6% of the adolescent males assessed received
a score of 1–2. Because the behavioral assessment is
not administered to adolescent females, only adolescent
males were included in the current analysis.
This study was approved by the local institutional
Of 438 486 Israeli-born male adolescents consecutively
screened by the Israeli Draft, 96.9% had valid data on
parental age at birth. We excluded 4.7% who had missing
or incomplete data on the medical, including psychiatric,
assessment, and 8.8% who had missing data for social
functioning. The final analytic sample included, there-
fore, 403 565 Israeli-born male adolescents.
For purposes of analysis, social functioning was treated
as dichotomous variable, comparing those male adoles-
cents with very poor or poor social functioning (1–2 on
the original scale) with those with adequate, good, or su-
perior social functioning (3–5 on the original scale).
Father’s ageat birth was treated as a categorical variable,
divided into 7 age categories: younger than 20 years,
20–24 years, 25–29 years (considered to be the reference
category), 30–34 years, 35–39 years, 40–44 years, and 45
years of age and above.17Mother’s age at birth was sim-
ilarly defined in 6 levels: younger than 20 years, 20–24
years, 25–29 years (considered to be the reference cate-
gory), 30–34 years, 35–39 years, 40 years and above.
Birth order, proband’s IQ, the other parent’s age at
time of birth, and socioeconomic status significantly af-
fected social functioning scores in this dataset (table 1
and 2); hence, they were added as covariates in the anal-
yses, all treated as continuous measures. Due to slight
variations in the draft board scoring of social functioning
over the years, we also included the year of the draft
board assessment as a covariate. Separate analyses
fined categorically as mentioned above).
Logistic regression was used to calculate the associa-
odds ratios (ORs) and 95% confidence intervals
(CIs), both before and after adjustment for potential
Multicollinearity was tested using Pearson correlation
and collinearity diagnostics provided by the multiple
factors—VIF—and tolerances. Analyses were conducted
using SPSS 15.0.
Unadjusted analyses showed an ‘‘U-shaped’’ pattern:
male adolescent children of fathers younger than 20 years
at birth had increased prevalence of poor social function-
ing scores (OR = 1.72, 95% CI = 1.49–1.98); male adoles-
cent children of fathers belonging to the oldest age group
(?45 years) were 1.71 (95% CI = 1.63–1.79) times more
likely to have poor social functioning compared with
male adolescent children of fathers aged 25–29 years at
birth. These results were slightly attenuated but remained
significant after controlling for potential confounders
Similar to father’s age, unadjusted analyses of the asso-
ciation between mother’s age and social functioning also
showed an ‘‘U-shaped’’ pattern: male adolescent children
of mothers younger than 20 years at birth had increased
prevalence of poor social functioning scores (OR = 1.21,
95% CI = 1.16–1.27), and male adolescent children of
mothers belonging to the oldest age group (?40 years)
Table 1. IQ and Socioeconomic Status (SES) Levels in Male Adolescents With Poor Vs Normal-High Social Functioning
Low Social Functioning Normal-High Social Functioning
MinimumMaximum Mean (SD) MinimumMaximum Mean (SD)
Parental Age and Social Functioning
were 1.61 (95% CI = 1.52–1.71) times more likely to have
poor social functioning compared with male adolescent
children of mothers aged 25–29 years at birth. This
U-shape distribution was lost when possible confounders
were entered into the analysis; male adolescent children
of mothers belonging to the oldest age group (?40 years)
were 1.15 (95% CI = 1.07–1.24) times more likely to have
poor social functioning compared with male adolescent
children of mothers aged 25–29 years at birth (table 3).
Pearson correlation indicated that father’s age at birth
was highly correlated with mother’s age at birth
(r = 0.79). Correlationsbetween
and father’s age were all r ? 0.5. The highest variance
inflation factors (VIF) score was 2.41 and the lowest tol-
erance score was 0.4 therefore collinearity scores are
within accepted ranges of multicollinearity.18,19
This population-based study found an ‘‘U-shaped’’ rela-
tionship between social functioning and father’s age at
birth, with male adolescent children of both younger
and older fathers having increased prevalence of poor so-
cial functioning. The increase in prevalence of poor social
of the evidence regarding father’s age and risk for schizo-
phrenia; one article17reported increased risk of schizo-
phrenia in children of younger fathers, with other
articles3,4reporting trends in the same direction. In-
creased risk for schizophrenia in children of older fathers
is a well-replicated finding,1–7and increased risk for
schizophrenia in children of older mothers has also
been reported in previous studies.5,11Advanced father’s
illness also characterized by impaired social functioning.
Impaired premorbid social functioning is strongly
associated with later schizophrenia,20and unaffected sib-
lings of patients with schizophrenia21and with autism22
have impaired social abilities that are intermediate be-
tween their affected brothers and population norms.
Thus, poor social functioning might represent a behav-
ioral expression of familial, perhaps increased, genetic
risk. It is conceivable that at least part of the effect of in-
creasing parental age on risk for schizophrenia and au-
tism is mediated by the relationship between increasing
parental age and poor social functioning. The biological
mechanism by which advanced father’s age affects social
functioning is not known. It is conceivable that the same
mechanisms evoked to explain the association between
increased father’s age at birth with schizophrenia are rel-
evant here. One explanation is that there is a higher fre-
quency of point mutations in males, the frequency of
which increases with age.23Other forms of mutation,
such as altered copy number in repeat DNA, and chro-
mosome breakage have also been related to male
High Social Functioning and Birth Order
Table 3. Association Between Father’s and Mother’s Age at Birth and Social Functioning in Male Adolescents
at Birth (y)
(N = 299 559)
(%) (N = 68 685)
Less than 20
Less than 20
aAdjusted analyses controlled for cognitive functioning, the other parent’s age, parental socioeconomic status, birth order, and draft
board year of assessment. OR, odds ratio; CI, confidence interval.
M. Weiser et al.
aging.24,25In addition, advancing age is associated with
dysregulation of epigenetic processes.26
The finding of poor social functioning in offspring of
very young fathers may also be related to their elevated
risk of de novo genetic disorders, which may result from
immaturity of spermatids or from low activity of DNA
repair or antioxidant enzymes.27
The association between advanced mother’s age and
poorer social functioning might involve nucleotide repeat
instability.28Trinucleotide or triplet repeats are 3 nucleo-
tides consecutively repeated within a region of DNA and
have been found to undergo a type of genetic mutation,
termed a ‘‘dynamic’’ or ‘‘expansion mutation.’’ In this
type of mutation, through mechanisms that occur during
DNA replication and are only partially understood, the
number of triplets in a repeat increases.29Unlike repeats
of normal length, in which length changes only rarely
from one generation to the next, expanded repeats
tend to be unstable and will typically become longer
over successive generations. Trinucleotide repeats are
more common in offspring of older, compared with
younger,women.28During the past decade, nearly 20dis-
eases caused by a trinucleotide repeat expansion have
been identified, as well as other diseases caused by related
mutations, including schizophrenia, autism, Huntington
disease, and fragile X syndrome.30,31
This study’s results are consistent with similar findings
other medical conditions and complex behavioral phe-
nomena in offspring32such as Apert syndrome,33
Down syndrome,34achodroplasia,35newborn death,36
birth weight,37diabetes,38and intelligence.39
Social functioning can be affected by many causes,
which might or might not be relevant for schizophrenia.
On one hand, impaired social functioning is certainly
a core symptom of patients with schizophrenia, and in
large historical prospective study, impairment on this
measure of social functioning was a strong predictor of
later schizophrenia (OR = 4), a much larger effect than,
for instance, low IQ.20Also, siblings of schizophrenia
patients have social functioning scores slightly below
those of normal controls.21On the other hand, there
are many possible sources of impaired social functioning,
both in schizophrenia and in adolescents without a diag-
nosable mental illness. One person might be suspicious
and afraid people want to hurt him, another desperately
wants social contact but is afraid of rejection, another
want social interactions but lack the appropriate social
skills to do so, etc. The data available here do not enable
us to parcel out these possibilities. Hence, although there
are good reasons to assume that the decrease in social
functioning caused by advanced parental age at birth in
the population is related to schizophrenia, there are prob-
ably other reasons not related to schizophrenia that play
a role in impaired social functioning as well.
These results are limited in that social functioning is
assessed only in males, and we cannot know what effect,
if any, increased paternal age has on social functioning in
females. This is particularly significant during adoles-
cence because gender-based differences in social func-
tioning are not unlikely at these ages. Regarding
schizophrenia, at least 2 of the articles published on
the topic of paternal age and schizophrenia2,5reported
that advanced father’s age at birth was associated with
increased risk for later schizophrenia both in male and
femaleoffspring; hence, itwould be reasonableto assume
that advanced parental age would be a poor social
functioning in females as well.
In summary, social functioning is worse in sons of very
young and of older parents. This effect is relatively small
(OR = 1.5) and is probably not clinically relevant. The
significance of this finding is conceptual, in that it implies
that very young and advanced parental age might in-
crease risk for schizophrenia via a slightly deleterious ef-
fect on social functioning. This finding is consistent with
a similar finding of advanced parental age having
a slightly deleterious effect on cognitive abilities.39Taken
together, these data further our understanding of risk for
schizophrenia, indicating that the risk pathway of ad-
vanced parental age on schizophrenia might, at least par-
tially, work via its mildly deleterious effects on social
functioning and cognition.
Stanley Medical Research Institute; National Institute of
Mental Health (5RO1MH066105-05 to M.D.).
The authors declare that they have no potential conflicts
1. Brown AS, Schaefer CA, Wyatt RJ, et al. Paternal age and
risk of schizophrenia in adult offspring. Am J Psychiatry.
2. Byrne M, Agerbo E, Ewald H, Eaton WW, Mortensen PB.
Parental age and risk of schizophrenia: a case-control study.
Arch Gen Psychiatry. 2003;60:673–678.
3. Dalman C, Allebeck P. Paternal age and schizophrenia: fur-
ther supportfor anassociation.
4. El-Saadi O, Pedersen CB, McNeil TF, et al. Paternal and
maternal age as risk factors for psychosis: findings from
Denmark, Sweden and Australia. Schizophr Res. 2004;67:
5. Malaspina D, Harlap S, Fennig S, et al. Advancing paternal
age and the risk of schizophrenia. Arch Gen Psychiatry.
6. Sipos A, Rasmussen F, Harrison G, et al. Paternal age and
schizophrenia: a population based cohort study. BMJ.
Parental Age and Social Functioning
7. Zammit S, Allebeck P, Dalman C, et al. Paternal age and risk
for schizophrenia. Br J Psychiatry. 2003;183:405–408.
8. Croen LA, Najjar DV, Fireman B, Grether JK. Maternal and
paternal age and risk of autism spectrum disorders. Arch
Pediatr Adolesc Med. 2007;161:334–340.
9. Lauritsen MB, Pedersen CB, Mortensen PB. Effects of famil-
ial risk factors and place of birth on the risk of autism: a
nationwide register-based study. J Child Psychol Psychiatry.
10. Reichenberg A, Gross R, Weiser M, et al. Advancing paternal
age and autism. Arch Gen Psychiatry. 2006;63:1026–1032.
11. Ekeus C, Olausson PO, Hjern A. Psychiatric morbidity is re-
lated to parental age: a national cohort study. Psychol Med.
12. Tan HY, Callicott JH, Weinberger DR. Intermediate pheno-
types in schizophrenia genetics redux: is it a no brainer? Mol
13. Blum K, Noble EP. Handbook of Psychiatric Genetics. Boca
Raton, Fla: CRC Press; 1997.
14. American Psychiatric Association Task Force on DSM-IV.
Diagnostic and Statistical Manual of Mental Disorders:
DSM-IV. 4th ed. Washington, DC: American Psychiatric
15. Gal R. The selection, classification and placement process: A
portrait of the Israeli soldier. Westport, Conn: Greenwood
16. Tubiana JH, Ben-Shachar G. An objective group question-
naire as a substitute for a personal interview in the prediction
of success in military training in Israel. Pers Psychol.
17. Wohl M, Gorwood P. Paternal ages below or above 35 years
old are associated with a different risk of schizophrenia in the
offspring. Eur Psychiatry. 2007;22:22–26.
18. Bowerman BL, O’Connell RT. Linear Statistical Models: An
Applied Approach. 2nd ed. Belmont, Calif: Duxbury; 1990.
19. Menard S. Applied Logistic Regression Analysis. Sage Univer-
sity Paper Series on Quantitative Applications in the Social
Sciences. Thousands Oaks, Calif: Sage; 1995.
20. Davidson M, Reichenberg A, Rabinowitz J, Weiser M,
Kaplan Z, Mark M. Behavioral and intellectual markers for
schizophrenia in apparently healthy male adolescents. Am J
21. Glatt SJ, Stone WS, Faraone SV, Seidman LJ, Tsuang MT.
Psychopathology, personality traits and social development
of young first-degree relatives of patients with schizophrenia.
Br J Psychiatry. 2006;189:337–345.
22. Constantino JN, Lajonchere C, Lutz M, et al. Autistic social
impairment in the siblings of children with pervasive develop-
mental disorders. Am J Psychiatry. 2006;163:294–296.
23. Crow JF. Spontaneous mutation in man. Mutat Res. 1999;
24. Ellegren H. Microsatellite mutations in the germline: implica-
tions for evolutionary inference. Trends Genet. 2000;16:
25. Singh NP, Muller CH, Berger RE. Effects of age on dna dou-
ble-strand breaks and apoptosis in human sperm. Fertil Steril.
26. Perrin MC, Brown AS, Malaspina D. Aberrant epigenetic
regulation could explain the relationship of paternal age to
schizophrenia. Schizophr Bull. 2007;33:1270–1273.
27. Malaspina D. Paternal factors and schizophrenia risk: de
novo mutations and imprinting. Schizophr Bull. 2001;27:
28. Kaytor MD, Burright EN, Duvick LA, Zoghbi HY, Orr HT.
Increased trinucleotide repeat instability with advanced
maternal age. Hum Mol Genet. 1997;6:2135–2139.
29. Pearson CE, Sinden RR. Slipped strand dna, dynamic muta-
tions, and human disease. In: Wells RD, Warren ST, (eds.)
Genetic Instabilities and Hereditary Neurological Diseases.
San Diego, California: Academic Press Inc; 1998:585–521.
30. Persico AM, D’Agruma L, Maiorano N, et al. Reelin gene
alleles and haplotypes as a factor predisposing to autistic dis-
order. Mol Psychiatry. 2001;6:150–159.
31. Zhang H, Liu X, Zhang C, et al. Reelin gene alleles and sus-
ceptibility to autism spectrum disorders. Mol Psychiatry.
32. Glaser RL, Jabs EW. Dear old dad. Sci Aging Knowledge
33. Glaser RL, Broman KW, Schulman RL, Eskenazi B,
Wyrobek AJ, Jabs EW. The paternal-age effect in Apert syn-
drome is due, in part, to the increased frequency of mutations
in sperm. Am J Hum Genet. 2003;73:939–947.
34. Fisch H, Hyun G, Golden R, Hensle TW, Olsson CA,
Liberson GL. The influence of paternal age on down syn-
drome. J Urol. 2003;169:2275–2278.
35. Tiemann-Boege I, Navidi W, Grewal R, et al. The observed
human sperm mutation frequency cannot explain the achon-
droplasia paternal age effect. Proc Natl Acad Sci USA. 2002;
36. Wunsch G, Gourbin C. Parents’ age at birth of their offspring
and child survival. Soc Biol. 2002;49:174–184.
37. Abel EL, Kruger M, Burd L. Effects of maternal and paternal
age on Caucasian and native American preterm births and
birth weights. Am J Perinatol. 2002;19:49–54.
38. Cardwell CR, Carson DJ, Patterson CC. Parental age at
delivery, birth order, birth weight and gestational age are
associated with the risk of childhood type 1 diabetes: a UK
regional retrospective cohort study. Diabet Med. 2005;22:
39. Malaspina D, Reichenberg A, Weiser M, et al. Paternal age
and intelligence: implications for age-related genomic changes
in male germ cells. Psychiatr Genet. 2005;15:117–125.
M. Weiser et al.