The sex-specific genetic architecture of quantitative traits in humans

Weiss, Lauren A.; Lin, Pao‐Hwa; Abney, Mark; Ober, Carole

doi:10.1038/ng1726

Cited by 374 publications

(313 citation statements)

References 28 publications

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“…Our results of no sex-specific genetic effects for BMI are in agreement with some family studies [18,19], but they are in contrast with twin studies that found higher [2,3,13,14], or lower [15][16][17] heritability estimates in women than in men. Schousboe et al [6] found slight differences between women and men in the extent of additive genetic and common environmental influences on BMI, anthropometric measures of fat distribution and fat% and LMI estimated by bioelectrical impedance in twins, but CIs were broad and overlapped for most estimates.…”

Section: Discussionsupporting

confidence: 90%

“…Studies on sex differences in heritability of BMI have shown inconsistent results. Some studies found evidence for a higher heritability of BMI in women than in men [2,3,[12][13][14] or the other way around [15][16][17] or no difference [18,19]. In the Diabetes Heart Study [7], heritability estimates were larger in women for BMI and lean mass but not for fat percentage (fat%) assessed by dual-energy x-ray absorptiometry (DXA).…”

Section: Introductionmentioning

confidence: 99%

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Sex-specific genetic effects influence variation in body composition

et al. 2008

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Aims/hypothesis Despite well-known sex differences in body composition it is not known whether sex-specific genetic or environmental effects contribute to these differences. Methods We assessed body composition in 2,506 individuals, from a young Dutch genetic isolate participating in the Erasmus Rucphen Family study, by dual-energy X-ray absorptiometry and anthropometry. We used variance decomposition procedures to partition variation of body composition into genetic and environmental components common to both sexes and to men and women separately and calculated the correlation between genetic components in men and women. Results After accounting for age, sex and inbreeding, heritability ranged from 0.39 for fat mass index to 0.84 for height. We found sex-specific genetic effects for fat percentage (fat%), lean mass, lean mass index (LMI) and fat distribution, but not for BMI and height. Genetic correlations between sexes were significantly different from 1 for fat%, lean mass, LMI, android fat, android:gynoid fat ratio and WHR, indicating that there are sex-specific genes contributing to variation of these traits. Genetic variance was significantly higher in women for the waist, hip and thigh circumference and WHR, implying that genes account for more variance of fat distribution in women than in men. Environmental variance was significantly higher in men for the android: gynoid fat ratio. Conclusions/interpretation Sex-specific genetic effects underlie sexual dimorphism in several body composition traits. The findings are relevant for studies on the relationship of body composition with common diseases like cardiovascular disease and type 2 diabetes and for genetic association studies.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Sex-specific genetic effects influence variation in body composition

et al. 2008

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“…mB Megabase *Genetic positions of markers showing the strongest evidence of linkage to lipid variables and 95% CIs were obtained from our high-density reference rat linkage map constructed in a GK×BN cross [13]. **Data derived following the integration of the rat genetic map in the rat genome sequence and comparative genome analyses (http://www.well.ox.ac.uk/rat_mapping_resources) [34]. We only report physical distances in the rat, mouse and human genomes (http://www.ensembl.org/Rattus_norvegicus/) for the 95% CI intervals of the most significant QTL.…”

Section: Discussionmentioning

confidence: 99%

Genetic control of plasma lipid levels in a cross derived from normoglycaemic Brown Norway and spontaneously diabetic Goto–Kakizaki rats

et al. 2006

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Aims/hypothesis Dyslipidaemia is a main component of the insulin resistance syndrome. The inbred Goto-Kakizaki (GK) rat is a model of spontaneous type 2 diabetes and insulin resistance, which has been used to identify diabetes-related susceptibility loci in genetic crosses. The objective of our study was to test the genetic control of lipid metabolism in the GK rat and investigate a possible relationship with known genetic loci regulating glucose homeostasis in this strain. Materials and methods Plasma concentration of triglycerides, phospholipids, total cholesterol, HDL, LDL and VLDL cholesterol were determined in a cohort of 151 hybrids of an F2 cross derived from GK and non-diabetic Brown Norway (BN) rats. Data from the genome-wide scan of the F2 hybrids were used to test for evidence of genetic linkage to the lipid quantitative traits. Results We identified statistically significant quantitative trait loci (QTLs) that control the level of plasma phospholipids and triglycerides (chromosome 1), LDL cholesterol (chromosome 3) and total and HDL cholesterol (chromosomes 1 and 5). These QTLs do not coincide with previously identified diabetes susceptibility loci in a similar cross. The significance of lipid QTLs mapped to chromosomes 1 and 5 is strongly influenced by sex. Conclusion/interpretation We established that several genetic loci control the quantitative variations of plasma lipid variables in a GK×BN cross. They appear to be distinct from known GK diabetes QTLs, indicating that lipid metabolism and traits directly relevant to glucose and insulin regulation are controlled by different gene variants in this strain combination.

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“…The aims were to quantify the relative roles of additive genetic and shared household effects in determining faecal egg counts of N. americanus and, given recent reports of sex-differences in heritabilities of a broad range of quantitative traits in humans (Weiss et al 2006), to explore the relative role of both factors in males and females.…”

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confidence: 99%

Heritability of human hookworm infection in Papua New Guinea

et al. 2008

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S U M M A R YHookworms infect approximately 740 million humans worldwide and are an important cause of morbidity. The present study examines the role of additive genetic effects in determining the intensity of hookworm infection in humans, and whether these effects vary according to the sex of the host. Parasitological and epidemiological data for a population of 704 subjects in Papua New Guinea were used in variance components analysis. The ' narrow-sense ' heritability of hookworm infection was estimated as 0 . 15¡0 . 04 (P<0 . 001), and remained significant when controlling for shared environmental (household) effects. Allowing the variance components to vary between the sexes of the human host consistently revealed larger additive genetic effects in females than in males, reflected by heritabilities of 0 . 18 in females and 0 . 08 in males in a conservative model. Household effects were also higher in females than males, although the overall household effect was not significant. The results indicate that additive genetic effects are an important determinant of the intensity of human hookworm infection in this population. However, despite similar mean and variance of intensity in each sex, the factors responsible for generating variation in intensity differ markedly between males and females.

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The sex-specific genetic architecture of quantitative traits in humans

Cited by 374 publications

References 28 publications

Sex-specific genetic effects influence variation in body composition

Sex-specific genetic effects influence variation in body composition

Genetic control of plasma lipid levels in a cross derived from normoglycaemic Brown Norway and spontaneously diabetic Goto–Kakizaki rats

Heritability of human hookworm infection in Papua New Guinea

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