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; Sarah E Medland; So-Youn Shin; Alan F Wright; James F Wilson; Wellcome Trust Case Control Consortium

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, Sarah E Medland, So-Youn Shin, Alan F Wright, James F Wilson, Wellcome Trust Case Control Consortium

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

30 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
Pages (from-to)	4805-15
Number of pages	11
Journal	Human Molecular Genetics
Volume	21
Issue number	21
DOIs	https://doi.org/10.1093/hmg/dds304
Publication status	Published - 1 Nov 2012

Keywords

European Continental Ancestry Group
Female
Gene Frequency
Genome-Wide Association Study
Humans
Male
Models, Genetic
Polymorphism, Single Nucleotide
Sex Factors
Sex Ratio
Sexism

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Boraska, V., Jerončić, A., Colonna, V., Southam, L., Nyholt, D. R., Rayner, N. W., 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., ... Wellcome Trust Case Control Consortium (2012). Genome-wide meta-analysis of common variant differences between men and women. Human Molecular Genetics, 21(21), 4805-15. https://doi.org/10.1093/hmg/dds304

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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.",

keywords = "European Continental Ancestry Group, Female, Gene Frequency, Genome-Wide Association Study, Humans, Male, Models, Genetic, Polymorphism, Single Nucleotide, Sex Factors, Sex Ratio, Sexism",

author = "Vesna Boraska and Ana Jeron{\v c}i{\'c} and Vincenza Colonna and Lorraine Southam and Nyholt, {Dale R} and Rayner, {Nigel William} 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 Zhao, {Jing Hua} and Jackson, {Anne U} and Jouke-Jan Hottenga and Antti Jula and Mika K{\"a}h{\"o}nen and Kay-Tee Khaw 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 Marja-Liisa Lokki and Christina Loley and Medland, {Sarah E} and So-Youn Shin and Wright, {Alan F} and Wilson, {James F} and {Wellcome Trust Case Control Consortium}",

year = "2012",

month = nov,

day = "1",

doi = "10.1093/hmg/dds304",

language = "English",

volume = "21",

pages = "4805--15",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

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}

Boraska, V, Jerončić, A, Colonna, V, Southam, L, Nyholt, DR, Rayner, NW, 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, Zhao, JH, Jackson, AU, Hottenga, J-J, Jula, A, Kähönen, M, Khaw, K-T, Kiemeney, LA, Klopp, N, Kutalik, Z, Lagou, V, Launer, LJ, Lehtimäki, T, Lemire, M, Lokki, M-L, Loley, C, Medland, SE, Shin, S-Y, Wright, AF, Wilson, JF & Wellcome Trust Case Control Consortium 2012, 'Genome-wide meta-analysis of common variant differences between men and women', Human Molecular Genetics, vol. 21, no. 21, pp. 4805-15. 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 - Rayner, Nigel William

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 - Zhao, Jing Hua

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 - Medland, Sarah E

AU - Shin, So-Youn

AU - Wright, Alan F

AU - Wilson, James F

AU - Wellcome Trust Case Control Consortium

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.

KW - European Continental Ancestry Group

KW - Female

KW - Gene Frequency

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Models, Genetic

KW - Polymorphism, Single Nucleotide

KW - Sex Factors

KW - Sex Ratio

KW - Sexism

U2 - 10.1093/hmg/dds304

DO - 10.1093/hmg/dds304

M3 - Article (Academic Journal)

C2 - 22843499

SN - 0964-6906

VL - 21

SP - 4805

EP - 4815

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 21

ER -

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

Abstract

Keywords

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