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

Authors:
Vesna Boraska, Ana Jerončić, Vincenza Colonna, Lorraine Southam, Dale R Nyholt, Nigel William Rayner, John R B Perry, Daniela Toniolo, Eva Albrecht, Wei Ang, Stefania Bandinelli, Maja Barbalic, Inês Barroso, Jacques S Beckmann, Reiner Biffar, Dorret Boomsma, Harry Campbell, Tanguy Corre, Jeanette Erdmann, Tõnu Esko, Krista Fischer, Nora Franceschini, Timothy M Frayling, Giorgia Girotto, Juan R Gonzalez, Tamara B Harris, Andrew C Heath, Iris M Heid, Wolfgang Hoffmann, Albert Hofman, Momoko Horikoshi, Jing Hua Zhao, Anne U Jackson, Jouke-Jan Hottenga, Antti Jula, Mika Kähönen, Kay-Tee Khaw, Lambertus A Kiemeney, Norman Klopp, Zoltán Kutalik, Vasiliki Lagou, Lenore J Launer, Terho Lehtimäki, Mathieu Lemire, Marja-Liisa Lokki, Christina Loley, Jian'an Luan, Massimo Mangino, Irene Mateo Leach, Sarah E Medland, Evelin Mihailov, Grant W Montgomery, Gerjan Navis, John Newnham, Markku S Nieminen, Aarno Palotie, Kalliope Panoutsopoulou, Annette Peters, Nicola Pirastu, Ozren Polasek, Karola Rehnström, Samuli Ripatti, Graham R S Ritchie, Fernando Rivadeneira, Antonietta Robino, Nilesh J Samani, So-Youn Shin, Juha Sinisalo, Johannes H Smit, Nicole Soranzo, Lisette Stolk, Dorine W Swinkels, Toshiko Tanaka, Alexander Teumer, Anke Tönjes, Michela Traglia, Jaakko Tuomilehto, Armand Valsesia, Wiek H van Gilst, Joyce B J van Meurs, Albert Vernon Smith, Jorma Viikari, Jacqueline M Vink, Gerard Waeber, Nicole M Warrington, Elisabeth Widen, Gonneke Willemsen, Alan F Wright, Brent W Zanke, Lina Zgaga, - -, Michael Boehnke, Adamo Pio d'Adamo, Eco de Geus, Ellen W Demerath, Martin den Heijer, Johan G Eriksson, Luigi Ferrucci, Christian Gieger, Vilmundur Gudnason, Caroline Hayward, Christian Hengstenberg, Thomas J Hudson, Marjo-Riitta Järvelin, Manolis Kogevinas, Ruth J F Loos, Nicholas G Martin, Andres Metspalu, Craig E Pennell, Brenda W Penninx, Markus Perola, Olli Raitakari, Veikko Salomaa, Stefan Schreiber, Heribert Schunkert, Tim D Spector, Michael Stumvoll, André G Uitterlinden, Sheila Ulivi, Pim van der Harst, Peter Vollenweider, Henry Völzke, Nicholas J Wareham, H-Erich Wichmann, James F Wilson, Igor Rudan, Yali Xue, Eleftheria Zeggini
Year of publication:
2012
Volume:
21
Issue:
21
Issn:
0964-6906
Journal title abbreviated:
HUM MOL GENET
Journal title long:
Human molecular genetics
Impact factor:
5.985
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.