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Genome-wide meta-analysis of common variant differences between men and women.

ABSTRACT: The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 × 10(-8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ~115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.

SUBMITTER: Boraska V

PROVIDER: S-EPMC3471397 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Genome-wide meta-analysis of common variant differences between men and women.

Boraska Vesna V Jerončić Ana A Colonna Vincenza V Southam Lorraine L Nyholt Dale R DR Rayner Nigel William NW Perry John R B JR Toniolo Daniela D Albrecht Eva E Ang Wei W Bandinelli Stefania S Barbalic Maja M Barroso Inês I Beckmann Jacques S JS Biffar Reiner R Boomsma Dorret D Campbell Harry H Corre Tanguy T Erdmann Jeanette J Esko Tõnu T Fischer Krista K Franceschini Nora N Frayling Timothy M TM Girotto Giorgia G Gonzalez Juan R JR Harris Tamara B TB Heath Andrew C AC Heid Iris M IM Hoffmann Wolfgang W Hofman Albert A Horikoshi Momoko M Zhao Jing Hua JH Jackson Anne U AU Hottenga Jouke-Jan JJ Jula Antti A Kähönen Mika M Khaw Kay-Tee KT Kiemeney Lambertus A LA Klopp Norman N Kutalik Zoltán Z Lagou Vasiliki V Launer Lenore J LJ Lehtimäki Terho T Lemire Mathieu M Lokki Marja-Liisa ML Loley Christina C Luan Jian'an J Mangino Massimo M Mateo Leach Irene I Medland Sarah E SE Mihailov Evelin E Montgomery Grant W GW Navis Gerjan G Newnham John J Nieminen Markku S MS Palotie Aarno A Panoutsopoulou Kalliope K Peters Annette A Pirastu Nicola N Polasek Ozren O Rehnström Karola K Ripatti Samuli S Ritchie Graham R S GR Rivadeneira Fernando F Robino Antonietta A Samani Nilesh J NJ Shin So-Youn SY Sinisalo Juha J Smit Johannes H JH Soranzo Nicole N Stolk Lisette L Swinkels Dorine W DW Tanaka Toshiko T Teumer Alexander A Tönjes Anke A Traglia Michela M Tuomilehto Jaakko J Valsesia Armand A van Gilst Wiek H WH van Meurs Joyce B J JB Smith Albert Vernon AV Viikari Jorma J Vink Jacqueline M JM Waeber Gerard G Warrington Nicole M NM Widen Elisabeth E Willemsen Gonneke G Wright Alan F AF Zanke Brent W BW Zgaga Lina L Boehnke Michael M d'Adamo Adamo Pio AP de Geus Eco E Demerath Ellen W EW den Heijer Martin M Eriksson Johan G JG Ferrucci Luigi L Gieger Christian C Gudnason Vilmundur V Hayward Caroline C Hengstenberg Christian C Hudson Thomas J TJ Järvelin Marjo-Riitta MR Kogevinas Manolis M Loos Ruth J F RJ Martin Nicholas G NG Metspalu Andres A Pennell Craig E CE Penninx Brenda W BW Perola Markus M Raitakari Olli O Salomaa Veikko V Schreiber Stefan S Schunkert Heribert H Spector Tim D TD Stumvoll Michael M Uitterlinden André G AG Ulivi Sheila S van der Harst Pim P Vollenweider Peter P Völzke Henry H Wareham Nicholas J NJ Wichmann H-Erich HE Wilson James F JF Rudan Igor I Xue Yali Y Zeggini Eleftheria E

Human molecular genetics 20120727 21

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-sc ...[more]

PMID: 22843499

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Project description:BackgroundThe principal aim of this study was to explore if biological differences between men and women can be explained by gendered mechanisms.MethodsWe used data from the 1958 National Child Development Study, including all the living subjects of the cohort at the outcome collection wave (44-45 years). We explored several biomarkers as outcomes: systolic blood pressure, triglycerides, LDL cholesterol, HbA1c, CRP, and cortisol. Three conceptualizations of gender have been used to define methodological strategies: (a) Gender as an individual characteristic; (b) Gender as an effect of sex on socio-behavioural characteristics; (c) Gender as an interaction between sex and the social environment, here the early-life social environment. We estimated the total effect of sex and the proportion of total effect of sex at birth eliminated by gender, measured by 3 different ways according to these 3 concepts, using g-computation.ResultsThe average level of each biomarker was significantly different according to sex at birth, higher in men for cardiometabolic biomarkers and higher in women for inflammatory and neuroendocrine biomarkers. The sizes of the differences were always smaller than one standard deviation but were larger than differences due to early-life deprivation, except for CRP. We observed gender mechanisms underlying these differences between men and women, even if the mediation effects were rarely statistically significant. These mechanisms were of three kinds: (1) mediation by socio-behavioural characteristics; (2) attenuation by gendered mechanisms; (3) interaction with early social environment. Indeed, we observed that being born into a deprived rather than non-deprived family increased metabolic and inflammatory biomarkers levels more strongly in females than in males.ConclusionsThe biological differences between men and women seem to not be purely explained by biological mechanisms. The exploration of gender mechanisms opens new perspectives, in terms of methodology, understanding and potential applications.

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Genome-wide meta-analysis of common variant differences between men and women.

Publications

Genome-wide meta-analysis of common variant differences between men and women.

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