1. Genome-wide meta-analysis of common variant differences between men and women
- Author
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Igor Rudan, Nora Franceschini, Sheila Ulivi, Maja Barbalić, Gérard Waeber, Jouke-Jan Hottenga, Jian'an Luan, James F. Wilson, Veikko Salomaa, Jacqueline M. Vink, Juan R. González, Aarno Palotie, Elisabeth Widen, Johan G. Eriksson, Alan F. Wright, Michael Stumvoll, Zoltán Kutalik, Caroline Hayward, Mathieu Lemire, Thomas J. Hudson, Johannes H. Smit, Gonneke Willemsen, Daniela Toniolo, Michael Boehnke, Olli T. Raitakari, Tanguy Corre, Dorret I. Boomsma, Harry Campbell, Stefania Bandinelli, Wiek H. van Gilst, Nigel W. Rayner, Kalliope Panoutsopoulou, Albert Hofman, Vasiliki Lagou, Alexander Teumer, Nicholas G. Martin, Dorine W. Swinkels, Jorma Viikari, Tamara B. Harris, Momoko Horikoshi, Massimo Mangino, Nicole M. Warrington, Kay-Tee Khaw, Adamo Pio D'Adamo, Lambertus A. Kiemeney, Tim D. Spector, Martin den Heijer, Evelin Mihailov, Wei Ang, Samuli Ripatti, Markus Perola, Nicola Pirastu, Ozren Polasek, Mika Kähönen, Albert V. Smith, Anke Tönjes, Michela Traglia, Jing Hua Zhao, Gerjan Navis, Christian Gieger, Stefan Schreiber, André G. Uitterlinden, Eva Albrecht, Inês Barroso, Marja-Liisa Lokki, Andrew C. Heath, Eco J. C. de Geus, H.-Erich Wichmann, Grant W. Montgomery, Armand Valsesia, Marjo-Riitta Järvelin, Reiner Biffar, Krista Fischer, Markku S. Nieminen, Jacques S. Beckmann, Ellen W. Demerath, Fernando Rivadeneira, Yali Xue, Vilmundur Gudnason, Christina Loley, Graham R. S. Ritchie, Giorgia Girotto, Lisette Stolk, Terho Lehtimäki, Annette Peters, Jeanette Erdmann, Lorraine Southam, Vincenza Colonna, So-Youn Shin, Andres Metspalu, Tõnu Esko, Craig E. Pennell, Jaakko Tuomilehto, Vesna Boraska, Nilesh J. Samani, Karola Rehnström, Antonietta Robino, Anne U. Jackson, Irene Mateo Leach, Nicholas J. Wareham, Manolis Kogevinas, Toshiko Tanaka, Heribert Schunkert, Sarah E. Medland, Juha Sinisalo, Wolfgang Hoffmann, John P. Newnham, Peter Vollenweider, Dale R. Nyholt, Lenore J. Launer, Luigi Ferrucci, Brent W. Zanke, Pim van der Harst, Ana Jerončić, Nicole Soranzo, Joyce B. J. van Meurs, Lina Zgaga, Christian Hengstenberg, Timothy M. Frayling, Eleftheria Zeggini, Iris M. Heid, Brenda W.J.H. Penninx, Norman Klopp, Ruth J. F. Loos, Antti Jula, Henry Völzke, John R. B. Perry, V., Boraska, A., Jeroncic, V., Colonna, L., Southam, D. R., Nyholt, N., William Rayner, J. R. B., Perry, D., Toniolo, E., Albrecht, W., Ang, S., Bandinelli, M., Barbalic, I., Barroso, J. S., Beckmann, R., Biffar, D., Boomsma, H., Campbell, T., Corre, J., Erdmann, T., Esko, K., Fischer, N., Franceschini, T. M., Frayling, Girotto, Giorgia, J. R., Gonzalez, T. B., Harri, A. C., Heath, I. M., Heid, W., Hoffmann, A., Hofman, M., Horikoshi, J., Hua Zhao, A. U., Jackson, J. J., Hottenga, A., Jula, M., Kahonen, K. T., Khaw, L. A., Kiemeney, N., Klopp, Z., Kutalik, V., Lagou, L. J., Launer, T., Lehtimaki, M., Lemire, M. L., Lokki, C., Loley, J., Luan, M., Mangino, I., Mateo Leach, S. E., Medland, E., Mihailov, G. W., Montgomery, G., Navi, J., Newnham, M. S., Nieminen, A., Palotie, K., Panoutsopoulou, A., Peter, Pirastu, Nicola, O., Polasek, K., Rehnstrom, S., Ripatti, G. R. S., Ritchie, F., Rivadeneira, Robino, Antonietta, N. J., Samani, S. Y., Shin, J., Sinisalo, J. H., Smit, N., Soranzo, L., Stolk, D. W., Swinkel, T., Tanaka, A., Teumer, A., Tonje, Traglia, Michela, J., Tuomilehto, A., Valsesia, W. H., van Gilst, J. B. J., van Meur, A. V., Smith, J., Viikari, J. M., Vink, G., Waeber, N. M., Warrington, E., Widen, G., Willemsen, A. F., Wright, B. W., Zanke, L., Zgaga, M., Boehnke, D'Adamo, ADAMO PIO, E., de Geu, E. W., Demerath, M., den Heijer, J. G., Eriksson, L., Ferrucci, C., Gieger, V., Gudnason, C., Hayward, C., Hengstenberg, T. J., Hudson, M. R., Jarvelin, M., Kogevina, R. J. F., Loo, N. G., Martin, A., Metspalu, C. E., Pennell, B. W., Penninx, M., Perola, O., Raitakari, V., Salomaa, S., Schreiber, H., Schunkert, T. D., Spector, M., Stumvoll, A. G., Uitterlinden, S., Ulivi, P., van der Harst, P., Vollenweider, H., Volzke, N. J., Wareham, H. E., Wichmann, J. F., Wilson, I., Rudan, Y., Xue, E., Zeggini, Biological Psychology, EMGO+ - Musculoskeletal Health, Medical Research Council (MRC), Psychiatry, Internal medicine, EMGO - Musculoskeletal health, Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Wellcome Trust Case Control Consortium, Surgery, Epidemiology, Medical Oncology, Internal Medicine, Hematology, Immunology, and Clinical Genetics
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Male ,Netherlands Twin Register (NTR) ,sex differences ,Iron metabolism Pathogenesis and modulation of inflammation [IGMD 7] ,Genome-wide association study ,Aetiology, screening and detection [ONCOL 5] ,DISEASE ,meta-analysi ,0302 clinical medicine ,5. Gender equality ,Gene Frequency ,Gender differences ,GWAS ,Genetics (clinical) ,SEX-RATIO ,11 Medical and Health Sciences ,Genetics ,Genetics & Heredity ,0303 health sciences ,Association Studies Articles ,General Medicine ,ASSOCIATION ,male-to-female sex ratio ,meta-analysis ,TIME ,HUMAN SEX-RATIO ,030220 oncology & carcinogenesis ,SIMULATION ,Female ,Wellcome Trust Case Control Consortium ,Life Sciences & Biomedicine ,Sex ratio ,Biochemistry & Molecular Biology ,GENES ,BIRTH ,European Continental Ancestry Group ,Sexism ,Single-nucleotide polymorphism ,Biology ,Human sex ratio ,Polymorphism, Single Nucleotide ,White People ,03 medical and health sciences ,Sex Factors ,Humans ,Sex Ratio ,Allele ,Molecular Biology ,Allele frequency ,Health aging / healthy living Cardiovascular diseases [IGMD 5] ,030304 developmental biology ,Genetic association ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,Science & Technology ,Models, Genetic ,ta3121 ,06 Biological Sciences ,Minor allele frequency ,Genome-Wide Association Study - Abstract
Item does not contain fulltext 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 x 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 approximately 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.
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- 2012
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