Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22843499
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.
DATE PUBLISHED
2012 Nov 1
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2012/07/27
aheadofprint 2012/08/17
entrez 2012/07/31 06:00
pubmed 2012/07/31 06:00
medline 2013/04/04 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Boraska V Boraska Vesna V Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. vboraska@mefst.hr
Jerončić A Jerončić Ana A
Colonna V Colonna Vincenza V
Southam L Southam Lorraine L
Nyholt DR Nyholt Dale R DR
Rayner NW Rayner Nigel William NW
Perry JR Perry John R B JR
Toniolo D Toniolo Daniela D
Albrecht E Albrecht Eva E
Ang W Ang Wei W
Bandinelli S Bandinelli Stefania S
Barbalic M Barbalic Maja M
Barroso I Barroso Inês I
Beckmann JS Beckmann Jacques S JS
Biffar R Biffar Reiner R
Boomsma D Boomsma Dorret D
Campbell H Campbell Harry H
Corre T Corre Tanguy T
Erdmann J Erdmann Jeanette J
Esko T Esko Tõnu T
Fischer K Fischer Krista K
Franceschini N Franceschini Nora N
Frayling TM Frayling Timothy M TM
Girotto G Girotto Giorgia G
Gonzalez JR Gonzalez Juan R JR
Harris TB Harris Tamara B TB
Heath AC Heath Andrew C AC
Heid IM Heid Iris M IM
Hoffmann W Hoffmann Wolfgang W
Hofman A Hofman Albert A
Horikoshi M Horikoshi Momoko M
Zhao JH Zhao Jing Hua JH
Jackson AU Jackson Anne U AU
Hottenga JJ Hottenga Jouke-Jan JJ
Jula A Jula Antti A
Kähönen M Kähönen Mika M
Khaw KT Khaw Kay-Tee KT
Kiemeney LA Kiemeney Lambertus A LA
Klopp N Klopp Norman N
Kutalik Z Kutalik Zoltán Z
Lagou V Lagou Vasiliki V
Launer LJ Launer Lenore J LJ
Lehtimäki T Lehtimäki Terho T
Lemire M Lemire Mathieu M
Lokki ML Lokki Marja-Liisa ML
Loley C Loley Christina C
Luan J Luan Jian'an J
Mangino M Mangino Massimo M
Mateo Leach I Mateo Leach Irene I
Medland SE Medland Sarah E SE
Mihailov E Mihailov Evelin E
Montgomery GW Montgomery Grant W GW
Navis G Navis Gerjan G
Newnham J Newnham John J
Nieminen MS Nieminen Markku S MS
Palotie A Palotie Aarno A
Panoutsopoulou K Panoutsopoulou Kalliope K
Peters A Peters Annette A
Pirastu N Pirastu Nicola N
Polasek O Polasek Ozren O
Rehnström K Rehnström Karola K
Ripatti S Ripatti Samuli S
Ritchie GR Ritchie Graham R S GR
Rivadeneira F Rivadeneira Fernando F
Robino A Robino Antonietta A
Samani NJ Samani Nilesh J NJ
Shin SY Shin So-Youn SY
Sinisalo J Sinisalo Juha J
Smit JH Smit Johannes H JH
Soranzo N Soranzo Nicole N
Stolk L Stolk Lisette L
Swinkels DW Swinkels Dorine W DW
Tanaka T Tanaka Toshiko T
Teumer A Teumer Alexander A
Tönjes A Tönjes Anke A
Traglia M Traglia Michela M
Tuomilehto J Tuomilehto Jaakko J
Valsesia A Valsesia Armand A
van Gilst WH van Gilst Wiek H WH
van Meurs JB van Meurs Joyce B J JB
Smith AV Smith Albert Vernon AV
Viikari J Viikari Jorma J
Vink JM Vink Jacqueline M JM
Waeber G Waeber Gerard G
Warrington NM Warrington Nicole M NM
Widen E Widen Elisabeth E
Willemsen G Willemsen Gonneke G
Wright AF Wright Alan F AF
Zanke BW Zanke Brent W BW
Zgaga L Zgaga Lina L
Wellcome Trust Case Control Consortium
Boehnke M Boehnke Michael M
d'Adamo AP d'Adamo Adamo Pio AP
de Geus E de Geus Eco E
Demerath EW Demerath Ellen W EW
den Heijer M den Heijer Martin M
Eriksson JG Eriksson Johan G JG
Ferrucci L Ferrucci Luigi L
Gieger C Gieger Christian C
Gudnason V Gudnason Vilmundur V
Hayward C Hayward Caroline C
Hengstenberg C Hengstenberg Christian C
Hudson TJ Hudson Thomas J TJ
Järvelin MR Järvelin Marjo-Riitta MR
Kogevinas M Kogevinas Manolis M
Loos RJ Loos Ruth J F RJ
Martin NG Martin Nicholas G NG
Metspalu A Metspalu Andres A
Pennell CE Pennell Craig E CE
Penninx BW Penninx Brenda W BW
Perola M Perola Markus M
Raitakari O Raitakari Olli O
Salomaa V Salomaa Veikko V
Schreiber S Schreiber Stefan S
Schunkert H Schunkert Heribert H
Spector TD Spector Tim D TD
Stumvoll M Stumvoll Michael M
Uitterlinden AG Uitterlinden André G AG
Ulivi S Ulivi Sheila S
van der Harst P van der Harst Pim P
Vollenweider P Vollenweider Peter P
Völzke H Völzke Henry H
Wareham NJ Wareham Nicholas J NJ
Wichmann HE Wichmann H-Erich HE
Wilson JF Wilson James F JF
Rudan I Rudan Igor I
Xue Y Xue Yali Y
Zeggini E Zeggini Eleftheria E
INVESTIGATORS
JOURNAL
VOLUME: 21
ISSUE: 21
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2012
MONTH: Nov
DAY: 1
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
076113 Wellcome Trust United Kingdom
089062/Z/09/Z Wellcome Trust United Kingdom
092447/Z/10/Z Wellcome Trust United Kingdom
095831 Wellcome Trust United Kingdom
098051 Wellcome Trust United Kingdom
89061/Z/09/Z Wellcome Trust United Kingdom
AA07535 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
CZB/4/710 Chief Scientist Office United Kingdom
DK062370 NIDDK NIH HHS United States
G0401527 Medical Research Council United Kingdom
G1000143 Medical Research Council United Kingdom
G1001799 Medical Research Council United Kingdom
HHSN268200625226C PHS HHS United States
HHSN268201100005C PHS HHS United States
HHSN268201100006C PHS HHS United States
HHSN268201100007C PHS HHS United States
HHSN268201100008C PHS HHS United States
HHSN268201100009C PHS HHS United States
HHSN268201100010C PHS HHS United States
HHSN268201100011C PHS HHS United States
HHSN268201100012C PHS HHS United States
HL65234 NHLBI NIH HHS United States
HL67466 NHLBI NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
LM010098 NLM NIH HHS United States
MC_PC_U127561128 Medical Research Council United Kingdom
MC_U106179471 Medical Research Council United Kingdom
MC_U127561128 Medical Research Council United Kingdom
MH081802 NIMH NIH HHS United States
MH66206 NIMH NIH HHS United States
MOP-82893 Canadian Institutes of Health Research Canada
N.1-AG-1-1 NIA NIH HHS United States
N.1-AG-1-2111 NIA NIH HHS United States
N01-AG-1-2100 NIA NIH HHS United States
N01-AG-5-0002 NIA NIH HHS United States
R01 MH059160 NIMH NIH HHS United States
R01HL086694 NHLBI NIH HHS United States
R01HL087641 NHLBI NIH HHS United States
R01HL59367 NHLBI NIH HHS United States
RR018787 NCRR NIH HHS United States
U01HG004402 NHGRI NIH HHS United States
U24 MH068457-06 NIMH NIH HHS United States
UL1RR025005 NCRR NIH HHS United States
Cancer Research UK United Kingdom
Intramural NIH HHS United States
Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
European Continental Ancestry Group genetics
Female genetics
Gene Frequency genetics
Genome-Wide Association Study genetics
Humans genetics
Male genetics
Models, Genetic genetics
Polymorphism, Single Nucleotide genetics
Sex Factors genetics
Sex Ratio genetics
Sexism genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3471397 NLM