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

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 Polašek; 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

doi:10.1093/hmg/dds304

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

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 EskoKrista 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 Polašek, 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

^*Corresponding author for this work

Clinic of Internal Medicine II - Cardiology

9 Citations (Scopus)

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.

Original language	English
Article number	dds304
Journal	Human Molecular Genetics
Volume	21
Issue number	21
Pages (from-to)	4805-4815
Number of pages	11
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/dds304
Publication status	Published - 01.11.2012

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10.1093/hmg/dds304

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Boraska, V., Jerončić, A., Colonna, V., Southam, L., Nyholt, D. R., William rayner, N., Perry, J. R. B., Toniolo, D., Albrecht, E., Ang, W., Bandinelli, S., Barbalic, M., Barroso, I., Beckmann, J. S., Biffar, R., Boomsma, D., Campbell, H., Corre, T., Erdmann, J., ... Zeggini, E. (2012). Genome-wide meta-analysis of common variant differences between men and women. Human Molecular Genetics, 21(21), 4805-4815. Article dds304. https://doi.org/10.1093/hmg/dds304

@article{eb05873ad3334c54bfda1b2224945d22,

title = "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.",

author = "Vesna Boraska and Ana Jeron{\v c}i{\'c} and Vincenza Colonna and Lorraine Southam and Nyholt, {Dale R.} and {William rayner}, Nigel and Perry, {John R.B.} and Daniela Toniolo and Eva Albrecht and Wei Ang and Stefania Bandinelli and Maja Barbalic and In{\^e}s Barroso and Beckmann, {Jacques S.} and Reiner Biffar and Dorret Boomsma and Harry Campbell and Tanguy Corre and Jeanette Erdmann and T{\~o}nu Esko and Krista Fischer and Nora Franceschini and Frayling, {Timothy M.} and Giorgia Girotto and Gonzalez, {Juan R.} and Harris, {Tamara B.} and Heath, {Andrew C.} and Heid, {Iris M.} and Wolfgang Hoffmann and Albert Hofman and Momoko Horikoshi and {Hua zhao}, Jing and Jackson, {Anne U.} and Hottenga, {Jouke Jan} and Antti Jula and Mika K{\"a}h{\"o}nen and Khaw, {Kay Tee} and Kiemeney, {Lambertus A.} and Norman Klopp and Zolt{\'a}n Kutalik and Vasiliki Lagou and Launer, {Lenore J.} and Terho Lehtim{\"a}ki and Mathieu Lemire and Lokki, {Marja Liisa} and Christina Loley and Jian'an Luan and Massimo Mangino and {Mateo leach}, Irene and Medland, {Sarah E.} and Evelin Mihailov and Montgomery, {Grant W.} and Gerjan Navis and John Newnham and Nieminen, {Markku S.} and Aarno Palotie and Kalliope Panoutsopoulou and Annette Peters and Nicola Pirastu and Ozren Pola{\v s}ek and Karola Rehnstr{\"o}m and Samuli Ripatti and Ritchie, {Graham R.S.} and Fernando Rivadeneira and Antonietta Robino and Samani, {Nilesh J.} and Shin, {So Youn} and Juha Sinisalo and Smit, {Johannes H.} and Nicole Soranzo and Lisette Stolk and Swinkels, {Dorine W.} and Toshiko Tanaka and Alexander Teumer and Anke T{\"o}njes and Michela Traglia and Jaakko Tuomilehto and Armand Valsesia and {Van gilst}, {Wiek H.} and {Van meurs}, {Joyce B.J.} and Smith, {Albert Vernon} and Jorma Viikari and Vink, {Jacqueline M.} and Gerard Waeber and Warrington, {Nicole M.} and Elisabeth Widen and Gonneke Willemsen and Wright, {Alan F.} and Zanke, {Brent W.} and Lina Zgaga and Michael Boehnke and D'Adamo, {Adamo Pio} and {De geus}, Eco and Demerath, {Ellen W.} and {Den Heijer}, Martin and Eriksson, {Johan G.} and Luigi Ferrucci and Christian Gieger and Vilmundur Gudnason and Caroline Hayward and Christian Hengstenberg and Hudson, {Thomas J.} and J{\"a}rvelin, {Marjo Riitta} and Manolis Kogevinas and Loos, {Ruth J.F.} and Martin, {Nicholas G.} and Andres Metspalu and Pennell, {Craig E.} and Penninx, {Brenda W.} and Markus Perola and Olli Raitakari and Veikko Salomaa and Stefan Schreiber and Heribert Schunkert and Spector, {Tim D.} and Michael Stumvoll and Uitterlinden, {Andr{\'e} G.} and Sheila Ulivi and {Van der harst}, Pim and Peter Vollenweider and Henry V{\"o}lzke and Wareham, {Nicholas J.} and Wichmann, {H. Erich} and Wilson, {James F.} and Igor Rudan and Yali Xue and Eleftheria Zeggini",

year = "2012",

month = nov,

day = "1",

doi = "10.1093/hmg/dds304",

language = "English",

volume = "21",

pages = "4805--4815",

journal = "Human Molecular Genetics",

issn = "0964-6906",

number = "21",

}

Boraska, V, Jerončić, A, Colonna, V, Southam, L, Nyholt, DR, William rayner, N, Perry, JRB, Toniolo, D, Albrecht, E, Ang, W, Bandinelli, S, Barbalic, M, Barroso, I, Beckmann, JS, Biffar, R, Boomsma, D, Campbell, H, Corre, T, Erdmann, J, Esko, T, Fischer, K, Franceschini, N, Frayling, TM, Girotto, G, Gonzalez, JR, Harris, TB, Heath, AC, Heid, IM, Hoffmann, W, Hofman, A, Horikoshi, M, Hua zhao, J, Jackson, AU, Hottenga, JJ, Jula, A, Kähönen, M, Khaw, KT, Kiemeney, LA, Klopp, N, Kutalik, Z, Lagou, V, Launer, LJ, Lehtimäki, T, Lemire, M, Lokki, ML, Loley, C, Luan, J, Mangino, M, Mateo leach, I, Medland, SE, Mihailov, E, Montgomery, GW, Navis, G, Newnham, J, Nieminen, MS, Palotie, A, Panoutsopoulou, K, Peters, A, Pirastu, N, Polašek, O, Rehnström, K, Ripatti, S, Ritchie, GRS, Rivadeneira, F, Robino, A, Samani, NJ, Shin, SY, Sinisalo, J, Smit, JH, Soranzo, N, Stolk, L, Swinkels, DW, Tanaka, T, Teumer, A, Tönjes, A, Traglia, M, Tuomilehto, J, Valsesia, A, Van gilst, WH, Van meurs, JBJ, Smith, AV, Viikari, J, Vink, JM, Waeber, G, Warrington, NM, Widen, E, Willemsen, G, Wright, AF, Zanke, BW, Zgaga, L, Boehnke, M, D'Adamo, AP, De geus, E, Demerath, EW, Den Heijer, M, Eriksson, JG, Ferrucci, L, Gieger, C, Gudnason, V, Hayward, C, Hengstenberg, C, Hudson, TJ, Järvelin, MR, Kogevinas, M, Loos, RJF, Martin, NG, Metspalu, A, Pennell, CE, Penninx, BW, Perola, M, Raitakari, O, Salomaa, V, Schreiber, S, Schunkert, H, Spector, TD, Stumvoll, M, Uitterlinden, AG, Ulivi, S, Van der harst, P, Vollenweider, P, Völzke, H, Wareham, NJ, Wichmann, HE, Wilson, JF, Rudan, I, Xue, Y & Zeggini, E 2012, 'Genome-wide meta-analysis of common variant differences between men and women', Human Molecular Genetics, vol. 21, no. 21, dds304, pp. 4805-4815. https://doi.org/10.1093/hmg/dds304

TY - JOUR

T1 - Genome-wide meta-analysis of common variant differences between men and women

AU - Boraska, Vesna

AU - Jerončić, Ana

AU - Colonna, Vincenza

AU - Southam, Lorraine

AU - Nyholt, Dale R.

AU - William rayner, Nigel

AU - Perry, John R.B.

AU - Toniolo, Daniela

AU - Albrecht, Eva

AU - Ang, Wei

AU - Bandinelli, Stefania

AU - Barbalic, Maja

AU - Barroso, Inês

AU - Beckmann, Jacques S.

AU - Biffar, Reiner

AU - Boomsma, Dorret

AU - Campbell, Harry

AU - Corre, Tanguy

AU - Erdmann, Jeanette

AU - Esko, Tõnu

AU - Fischer, Krista

AU - Franceschini, Nora

AU - Frayling, Timothy M.

AU - Girotto, Giorgia

AU - Gonzalez, Juan R.

AU - Harris, Tamara B.

AU - Heath, Andrew C.

AU - Heid, Iris M.

AU - Hoffmann, Wolfgang

AU - Hofman, Albert

AU - Horikoshi, Momoko

AU - Hua zhao, Jing

AU - Jackson, Anne U.

AU - Hottenga, Jouke Jan

AU - Jula, Antti

AU - Kähönen, Mika

AU - Khaw, Kay Tee

AU - Kiemeney, Lambertus A.

AU - Klopp, Norman

AU - Kutalik, Zoltán

AU - Lagou, Vasiliki

AU - Launer, Lenore J.

AU - Lehtimäki, Terho

AU - Lemire, Mathieu

AU - Lokki, Marja Liisa

AU - Loley, Christina

AU - Luan, Jian'an

AU - Mangino, Massimo

AU - Mateo leach, Irene

AU - Medland, Sarah E.

AU - Mihailov, Evelin

AU - Montgomery, Grant W.

AU - Navis, Gerjan

AU - Newnham, John

AU - Nieminen, Markku S.

AU - Palotie, Aarno

AU - Panoutsopoulou, Kalliope

AU - Peters, Annette

AU - Pirastu, Nicola

AU - Polašek, Ozren

AU - Rehnström, Karola

AU - Ripatti, Samuli

AU - Ritchie, Graham R.S.

AU - Rivadeneira, Fernando

AU - Robino, Antonietta

AU - Samani, Nilesh J.

AU - Shin, So Youn

AU - Sinisalo, Juha

AU - Smit, Johannes H.

AU - Soranzo, Nicole

AU - Stolk, Lisette

AU - Swinkels, Dorine W.

AU - Tanaka, Toshiko

AU - Teumer, Alexander

AU - Tönjes, Anke

AU - Traglia, Michela

AU - Tuomilehto, Jaakko

AU - Valsesia, Armand

AU - Van gilst, Wiek H.

AU - Van meurs, Joyce B.J.

AU - Smith, Albert Vernon

AU - Viikari, Jorma

AU - Vink, Jacqueline M.

AU - Waeber, Gerard

AU - Warrington, Nicole M.

AU - Widen, Elisabeth

AU - Willemsen, Gonneke

AU - Wright, Alan F.

AU - Zanke, Brent W.

AU - Zgaga, Lina

AU - Boehnke, Michael

AU - D'Adamo, Adamo Pio

AU - De geus, Eco

AU - Demerath, Ellen W.

AU - Den Heijer, Martin

AU - Eriksson, Johan G.

AU - Ferrucci, Luigi

AU - Gieger, Christian

AU - Gudnason, Vilmundur

AU - Hayward, Caroline

AU - Hengstenberg, Christian

AU - Hudson, Thomas J.

AU - Järvelin, Marjo Riitta

AU - Kogevinas, Manolis

AU - Loos, Ruth J.F.

AU - Martin, Nicholas G.

AU - Metspalu, Andres

AU - Pennell, Craig E.

AU - Penninx, Brenda W.

AU - Perola, Markus

AU - Raitakari, Olli

AU - Salomaa, Veikko

AU - Schreiber, Stefan

AU - Schunkert, Heribert

AU - Spector, Tim D.

AU - Stumvoll, Michael

AU - Uitterlinden, André G.

AU - Ulivi, Sheila

AU - Van der harst, Pim

AU - Vollenweider, Peter

AU - Völzke, Henry

AU - Wareham, Nicholas J.

AU - Wichmann, H. Erich

AU - Wilson, James F.

AU - Rudan, Igor

AU - Xue, Yali

AU - Zeggini, Eleftheria

PY - 2012/11/1

Y1 - 2012/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84867814813&partnerID=8YFLogxK

U2 - 10.1093/hmg/dds304

DO - 10.1093/hmg/dds304

M3 - Journal articles

C2 - 22843499

AN - SCOPUS:84867814813

SN - 0964-6906

VL - 21

SP - 4805

EP - 4815

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 21

M1 - dds304

ER -

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

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