Ellen W Demerath

University of Minnesota Duluth, Duluth, Minnesota, United States

Are you Ellen W Demerath?

Claim your profile

Publications (128)759.33 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Studies from developed societies have shown that individuals with short legs relative to height have higher risk of type 2 diabetes. This has been much less explored in less developed populations where influences on relative leg length and diabetes may differ. The Brazilian Longitudinal Study of Adult Health (in Portuguese, ELSA-Brasil) allows us to test, in a cohort born (1934–1975) and raised when undernutrition was common, whether short legs relative to height is positively associated with diabetes, independent of early-life factors, including birth weight, age at menarche, and young-adult BMI.Methods We used baseline, cross-sectional data from 15,105 participants aged 35–74 years participating in ELSA-Brasil. We created age-and-sex-specific Z scores for leg length index (leg length/height × 100) according to an external reference. Diabetes was defined by self-reported physician diagnosis, medication use, fasting and 2-h post-75-g-load glucose, and A1C.ResultsA one-unit decrement in leg-length-index Z score was associated with 12% (8–17%) higher prevalence of diabetes in Brazilian adults, after adjustment through Poisson regression for confounders, including race, maternal education, and birth weight. This association persisted after further adjustment for menarche age, BMI (at age 20), buttocks circumference, and waist circumference. It was stronger among women with early menarche (P interaction = 0.02). Leg length index was also inversely associated with fasting glucose, fasting insulin, 2-h glucose, and A1C (P < 0.05).Conclusions In contemporary Brazilian adults, short legs relative to height is positively associated with diabetes independent of measures of intrauterine growth, pubertal timing, and young-adult adiposity. This association is stronger in women with early menarche. Am. J. Hum. Biol., 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.
    American Journal of Human Biology 10/2014; · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: DNA methylation is a widely studied epigenetic phenomenon; alterations in methylation patterns influence human phenotypes and risk of disease. As part of the Atherosclerosis Risk in Communities (ARIC) study, the Illumina Infinium HumanMethylation450 (HM450) BeadChip was used to measure DNA methylation in peripheral blood obtained from ~3000 African American study participants. Over 480,000 cytosine-guanine (CpG) dinucleotide sites were surveyed on the HM450 BeadChip. To evaluate the impact of technical variation, 265 technical replicates from 130 participants were included in the study.
    BMC Bioinformatics 09/2014; 15(1):312. · 3.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate whether greater cardiorespiratory fitness (CRF) is associated with better cognitive function 25 years later. We studied 2,747 participants in the community-based Coronary Artery Risk Development in Young Adults Study of black and white men and women aged 18 to 30 years at recruitment in 1985-1986 (baseline year 0). Symptom-limited maximal treadmill test durations at years 0 and 20 provided measures of CRF. Cognitive tests at year 25 measured verbal memory (Rey Auditory Verbal Learning Test [RAVLT]), psychomotor speed (Digit Symbol Substitution Test [DSST]), and executive function (Stroop Test). Per minute of baseline CRF, the RAVLT was 0.12 words recalled higher (standard error [SE] = 0.03, p < 0.0001), the DSST was 0.92 digits higher (SE = 0.13, p < 0.0001), and the Stroop Test score was 0.52 lower (better performance, SE = 0.11, p < 0.0001), after accounting for race, sex, age, education, and clinical center. Compared with the lowest quartile of CRF, each cognitive test was 21% to 34% of an SD better in the highest CRF quartile. Further adjustment for lifestyle and clinical measures attenuated coefficients for RAVLT and DSST slightly, while the coefficient predicting the Stroop Test lost more than half its value (p = 0.07). Analysis in the subset of 1,957 participants who also completed the year-20 treadmill test showed that 20-year change in CRF was positively associated only with DSST (p < 0.001). Better verbal memory and faster psychomotor speed at ages 43 to 55 years were clearly associated with better CRF 25 years earlier.
    Neurology 04/2014; · 8.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Age at menopause marks the end of a woman¡¦s reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified twenty-seven loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from eleven studies across the United States. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (p-value <0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of fourteen loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in United States.
    Human Molecular Genetics 02/2014; · 7.69 Impact Factor
  • Source
    S E Ramel, H L Gray, B A Davern, E W Demerath
    [Show abstract] [Hide abstract]
    ABSTRACT: The American Academy of Pediatrics calls for aggressive management of preterm infants to achieve body composition approximating that of the healthy infant in utero. Air displacement plethysmography (ADP) has been validated for assessment of body composition in preterm infants and could be used to monitor their nutritional status during hospitalization. Comparative datasets on body composition at birth among healthy, live-born preterm infants are lacking. The aim of this study is to provide the first descriptive fat mass (FM) and fat-free mass (FFM) data from healthy newborn preterm infants at birth as a proxy for healthy in utero body composition. Body mass and volume were obtained using ADP within 72 h of birth in 98 singleton, appropriate-for-gestational-age preterm infants. FM and FFM were calculated using the Fomon equation. Measurement with ADP was feasible and well tolerated by infants as young as 30 weeks gestation and <72 h of age. FFM and FM increased linearly over the gestational age range period at rates of 171 and 46 g week(-1) , respectively. Mean values obtained by ADP by gestational week were similar to the previously published reference data from chemical analysis on stillbirths. Body composition assessment using ADP is feasible in newborn preterm infants and provides group estimates similar to that of the reference fetus. In the future, integrating body composition information into the nutritional management of preterm infants may help to identify new strategies to optimize growth and development in this vulnerable population.
    Pediatric Obesity 01/2014; · 2.28 Impact Factor
  • Ellen W Demerath, David A Fields
    [Show abstract] [Hide abstract]
    ABSTRACT: Body composition assessment provides a sharper picture of the human biological response to genetic and environmental influences than measures of body size and weight. Infant body composition is particularly important as a marker of fetal adaptation and developmental programming of subsequent health and disease, but until recently, the range of options for measuring infant body composition was relatively narrow. The purpose of this Toolkit: Methods in Human Biology review is to provide a comprehensive overview of methods of body composition methods currently used in infants 0 to 2 years of age, including anthropometric prediction equations, air displacement plethysmography (ADP), dual energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), isotope dilution, and magnetic resonance imaging (MRI). Information on the reliability, validity, and accuracy of the methods is provided. Unique aspects of infant physiology and behavior create challenges for body composition assessment, but this review provides guidance on suitable testing approaches and environments that may aid researchers in this important area of investigation. Am. J. Hum. Biol., 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Human Biology 01/2014; · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
    Nature 01/2014; 514(7520):92-7. · 38.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β ± SE, 0.048 ± 0.008, P = 7.7 × 10(-9)) as was rs7302703-G in HOXC10 (β = 0.044 ± 0.008, P = 2.9 × 10(-7)) and rs936108-C in PEMT (β = 0.035 ± 0.007, P = 1.9 × 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 ± 0.02, P = 1.9 × 10(-6)) and rs1037575-A in ATBDB4 (β = 0.046 ± 0.01, P = 2.2 × 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.
    Human Molecular Genetics 12/2013; · 7.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Preterm infants are at risk for long-term neurodevelopmental impairment as a function of postnatal nutritional status. Despite adequate neonatal weight gain, preterm infants have altered body composition, with lower fat-free mass (FFM) and higher adiposity at term corrected gestational age (CGA) than their term counterparts. The relationship between postnatal body composition and speed of brain processing in preterm infants is unknown.Methods:Anthropometric measurements and body composition testing via air displacement plethysmography were performed on 16 appropriate for gestational age preterm (mean gestational age 30.4 +/- 2.8 weeks) infants at term and 4 months CGA. Infant visual pathway development was assessed at 4 months CGA using pattern-reversal visual evoked potential (VEP); P100 (positive peak) latency was used to index neuronal speed of processing.Results:Increased FFM at discharge (p=0.02) and 4 months CGA (p=0.006) were associated with shorter latencies to the P100 peak. P100 latency was not related to total body weight, fat mass, or percent body fat.Conclusions:FFM reflects protein accretion and indexes organ growth including the brain. The association of shorter VEP latency (i.e., faster neuronal processing) with higher FFM (i.e., better protein status) may be attributed to the positive effects of protein status on neuronal growth and differentiation.Pediatric Research (2013); doi:10.1038/pr.2013.138.
    Pediatric Research 08/2013; · 2.67 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10(-6) were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10(-8); RREB1: p = 5.7×10(-8)). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.
    PLoS Genetics 08/2013; 9(8):e1003681. · 8.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is biological crosstalk between insulin signaling and bone remodeling pathways, and wrist circumference and bone area were recently found to associate with insulin resistance independent of body mass index (BMI) in overweight/obese children. We aimed to expand on this work by using more specific measures of adiposity for adjustment and examining children with broader range of BMI. We used serial data (1,051 total measures) on 313 non-Hispanic white youth (ages 8-18 y) from the Fels Longitudinal Study with homeostasis model assessment of insulin resistance (HOMA-IR) as the outcome. Internal standard deviation score (SDS) for wrist breadth was evaluated as a predictor of HOMA-IR (log-transformed) before and after adjusting for internal-sample SDSs for BMI, waist circumference (WC), and total body fat (TBF) from dual energy X-ray absorptiometry, in addition to age, sex, Tanner stage, and birth year, using generalized estimating equations. Before additional adiposity adjustment, we found a significant positive association between wrist breadth SDS and log-transformed HOMA-IR (β = 0.13; 95%CI: 0.09-0.17), which remained significant after adjusting for TBF SDS (β = 0.09; 95%CI: 0.05-0.13; P < 0.001), BMI SDS (β = 0.06; 95%CI: 0.02-0.10; P = 0.007), and WC SDS (β = 0.06; 95%CI: 0.02-0.09; P = 0.005). Further work is needed to determine whether simple frame size measures such as wrist breadth may be useful markers of metabolic risk. Am. J. Hum. Biol., 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Human Biology 07/2013; · 2.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE:To investigate the association between early hyperglycemia and growth and development from hospital discharge to 2 years corrected age (CA) in very low birth weight (VLBW) infants.STUDY DESIGN:Blood glucose levels during the first 14 days after birth, weight, length and occipital-frontal circumference (OFC) at birth, hospital discharge and 4, 12 and 24 months CA, Bayley developmental scores at 12 and 24 months CA, and information on multiple clinical variables were recorded on VLBW preterm infants (N=80). The relationships between hyperglycemia, growth and developmental scores were determined using linear mixed effects regression.RESULT:Hyperglycemia was a strong predictor of poor rate of increase in weight, length and OFC until 24 months CA. Hyperglycemia was not associated with lower scores on the Bayley scales.CONCLUSION:Neonatal hyperglycemia was associated with poor physical growth until at least 2 years CA in this cohort of VLBW preterm infants.Journal of Perinatology advance online publication, 11 July 2013; doi:10.1038/jp.2013.77.
    Journal of perinatology: official journal of the California Perinatal Association 07/2013; · 1.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Genome wide association studies have shown 32 loci to influence BMI in European-American adults but replication in other studies is inconsistent and may be attributed to gene-by-age effects. The aims of this study were to determine if the influence of the summed risk score of these 32 loci (GRS) on BMI differed across age from birth to 40 years, and to determine if additive genetic effects other than those in the GRS differed by age. Design and Methods: Serial measures of BMI were calculated at 0, 1, 3, 6, 9, 12, 18, 28 months, and 4, 7, 11, 15, 19, 23, 30, and 40 years for 1176 (605 females, 571 males) European-American participants in the Fels Longitudinal Study. SOLAR was used for genetic analyses. Results: GRS was significant (p< 0.05) at ages: 6, 9 months, 4-15 years, and 23-40 years. Remaining additive genetic effects independently influenced BMI (p<5.3x10(-5) , 0.40<h(2) <0.76). Some genetic correlations between ages were not significant. Differential GRS effects did not retain significance after multiple comparisons adjustments. Conclusions: While well-known BMI variants do not appear to have significant differential effects, other additive genes differ over the lifespan.
    Obesity 06/2013; · 3.92 Impact Factor
  • Ellen W Demerath, William Johnson
    American Journal of Clinical Nutrition 05/2013; · 6.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To characterize an early trait in the BMI-for-age curve, the infant BMI peak. BMI-for-age curves were produced for 747 non-Hispanic, white Fels Longitudinal Study participants, from which individual age (AgePeak ) and BMI (BMIPeak ) at maximum infant BMI were estimated. Multivariable general linear regression was used to examine the effects of sex and birth year cohort (1929-1950, 1951-1970, and 1971-2010) on AgePeak and BMIPeak , with associations between BMIPeak and concurrent sum of four skinfold thicknesses assessed in a subsample (N = 155). Heritability (h(2) ) of AgePeak and BMIPeak was estimated using maximum-likelihood variance components analysis. AgePeak occurred at 9 months of age in both sexes, but BMIPeak was 0.4 kg/m(2) higher for boys than for girls (P-value < 0.001). Infants born between 1971 and 2010 experienced a 1.5 month earlier AgePeak and a 0.35 kg/m(2) lower BMIPeak than infants born between 1929 and 1950 (P-values < 0.001). Skinfold thickness explained 37% of the variance in BMIPeak in boys and 20% of the variance in girls (p-values < 0.001). AgePeak and BMIPeak were significantly heritable (h(2) = 0.54 and 0.75, respectively). Both AgePeak and BMIPeak decreased over successive birth year cohorts in the Fels Longitudinal Study. Despite a positive association of BMIPeak with concurrent adiposity, AgePeak appears to occur later than does the well-documented peak in infant fat mass and BMIPeak does not capture known sex differences in infant adiposity. Strong heritability of these infant BMI traits suggests investigation of genetic control, and validation of their relationship to body composition is greatly needed. Am. J. Hum. Biol. 25:378-388, 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Human Biology 05/2013; 25(3):378-88. · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: African American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association of self-reported age at menarche with common single nucleotide polymorphisms (SNPs) in a total of 18,089 AA women in 15 cohort studies using an additive genetic linear regression model, adjusting for year of birth and population stratification, followed by inverse-variance weighted meta-analysis (Stage 1). Top meta-analysis results were then tested in an independent sample of 2,850 women (Stage 2). First, while no SNP passed the pre-specified p< 5 x 10(-8) threshold for significance in Stage 1, suggestive associations were found for variants near FLRT2 and PIK3R1, and conditional analysis identified two independent SNPs (rs339978 and rs980000) in or near RORA, strengthening the support for this suggestive locus identified in EA women. Second, an investigation of SNPs in 42 previously identified menarche loci in EA women demonstrated that 25 (60%) of them contained variants significantly associated with menarche in AA women. The findings provide the first evidence of cross-ethnic generalization of menarche loci identified to date, and suggest a number of novel biological links to menarche timing in AA women.
    Human Molecular Genetics 04/2013; · 7.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10-11) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10-10). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10-8). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10-7), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.
    Nature Genetics 04/2013; · 35.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)(2)), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (1970-2010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 9-17 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.
    American journal of epidemiology 04/2013; · 5.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early menopause affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of early menopause is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies in 3493 early menopause cases and 13598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait were also associated with early menopause and POI (Primary Ovarian Insufficiency). Thus early menopause has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the SNP arrays was estimated to account for approximately 30% of the variance in EM. The association between the combined 17 variants and the risk of early menopause was greater than the best validated non-genetic risk factor, smoking.
    Human Molecular Genetics 01/2013; · 7.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is unclear whether earlier age at menarche is associated with higher body mass index (BMI) because they share a common genetic underpinning. We investigated the impact of single nucleotide polymorphisms (SNPs) influencing menarche timing on peripubertal BMI. For 556 Fels Longitudinal Study children (277 boys/279 girls) born 1928-1992, a genetic risk score (GRS(42) ) was computed as the sum of the number of risk alleles in 42 putative menarche SNPs. Serial BMI Z-scores within ±6.99 years from each individual's age at peak height velocity (Age@PHV) were grouped into seven time points (-6 years, -4 years, -2 years, Age@PHV, +2 years, +4years, and +6 years). Heritability of BMI ranged from 0.53 to 0.85 across the time points. The effect of GRS(42) on BMI Z-scores at each time point was modeled using variance components-based procedures. GRS(42) had a significant (P < 0.05) effect at every time point; an increase of one risk allele was associated with an increase of 0.03-0.08 BMI Z-scores. A separate score (GRS(29) ) was computed that excluded 13 of the menarche SNPs previously documented to also influence adiposity; significant main effects were observed at Age@PHV+4 and +6 years. This finding supports a causal effect of advanced sexual development on post-Age@PHV BMI. Significant positive GRS(42) (or GRS(29) )-by-birth year interactions indicate that some genetic influences on BMI have amplified over the 20th century. This gene-by-environment interaction also suggests that children with a genetic predisposition to earlier sexual development might avoid elevated BMI through alteration of their nutritional environment. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.
    American Journal of Physical Anthropology 01/2013; 150(1):10-20. · 2.48 Impact Factor

Publication Stats

2k Citations
759.33 Total Impact Points

Institutions

  • 2008–2014
    • University of Minnesota Duluth
      • Department of Family Medicine and Community Health
      Duluth, Minnesota, United States
  • 1999–2013
    • Wright State University
      • Department of Community Health
      Dayton, OH, United States
  • 2012
    • University of Iowa
      • Department of Pediatrics
      Iowa City, IA, United States
  • 2007–2012
    • University of Minnesota Twin Cities
      • • Department of Anthropology
      • • Division of Epidemiology and Community Health
      Minneapolis, MN, United States
    • Ohio University
      • Department of Social Medicine
      Athens, OH, United States
  • 2011
    • Montreal Heart Institute
      Montréal, Quebec, Canada
  • 2005
    • Harvard University
      • Department of Anthropology
      Cambridge, MA, United States
  • 2002
    • Loughborough University
      • Centre for Global Health and Human Development
      Loughborough, ENG, United Kingdom