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Assessment of gene‐by‐sex interaction effect on bone mineral density
Author(s) -
Liu ChingTi,
Estrada Karol,
YergesArmstrong Laura M,
Amin Najaf,
Evangelou Evangelos,
Li Guo,
Minster Ryan L,
Carless Melanie A,
Kammerer Candace M,
Oei Ling,
Zhou Yanhua,
Alonso Nerea,
Dailiana Zoe,
Eriksson Joel,
GarcíaGiralt Natalia,
Giroux Sylvie,
Husted Lise Bjerre,
Khusainova Rita I,
Koromila Theodora,
Kung Annie WaiChee,
Lewis Joshua R,
Masi Laura,
MencejBedrac Simona,
Nogues Xavier,
Patel Millan S,
Prezelj Janez,
Richards J Brent,
Sham Pak Chung,
Spector Timothy,
Vandenput Liesbeth,
Xiao SuMei,
Zheng HouFeng,
Zhu Kun,
Balcells Susana,
Brandi Maria Luisa,
Frost Morten,
Goltzman David,
GonzálezMacías Jesús,
Karlsson Magnus,
Khusnutdinova Elza K,
Kollia Panagoula,
Langdahl Bente Lomholt,
Ljunggren Östen,
Lorentzon Mattias,
Marc Janja,
Mellström Dan,
Ohlsson Claes,
Olmos José M,
Ralston Stuart H,
Riancho José A,
Rousseau François,
Urreizti Roser,
Van Hul Wim,
Zarrabeitia María T,
CastanoBetancourt Martha,
Demissie Serkalem,
Grundberg Elin,
Herrera Lizbeth,
Kwan Tony,
MedinaGómez Carolina,
Pastinen Tomi,
Sigurdsson Gunnar,
Thorleifsson Gudmar,
vanMeurs Joyce BJ,
Blangero John,
Hofman Albert,
Liu Yongmei,
Mitchell Braxton D,
O'Connell Jeffrey R,
Oostra Ben A,
Rotter Jerome I,
Stefansson Kari,
Streeten Elizabeth A,
Styrkarsdottir Unnur,
Thorsteinsdottir Unnur,
Tylavsky Frances A,
Uitterlinden Andre,
Cauley Jane A,
Harris Tamara B,
Ioannidis John PA,
Psaty Bruce M,
Robbins John A,
Zillikens M Carola,
vanDuijn Cornelia M,
Prince Richard L,
Karasik David,
Rivadeneira Fernando,
Kiel Douglas P,
Cupples L Adrienne,
Hsu YiHsiang
Publication year - 2012
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.1679
Subject(s) - expression quantitative trait loci , single nucleotide polymorphism , genome wide association study , biology , quantitative trait locus , genetics , gene , bone mineral , locus (genetics) , femoral neck , sexual dimorphism , genome , sex characteristics , bone density , osteoporosis , endocrinology , genotype
Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene‐by‐sex autosomal interactions genome‐wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome‐wide meta‐analysis of gene‐by‐sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single‐nucleotide polymorphisms (SNPs; p < 1 × 10 −5 ) in an additional set of 24,763 individuals. Gene‐by‐sex interaction and sex‐specific effects were examined in these 12 SNPs. We detected one novel genome‐wide significant interaction associated with LS‐BMD at the Chr3p26.1‐p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10 −5 ; female effect = −0.007 and p = 3.3 × 10 −2 ), and 11 suggestive loci associated with either FN‐ or LS‐BMD in discovery cohorts. However, there was no evidence for genome‐wide significant ( p < 5 × 10 −8 ) gene‐by‐sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome‐wide significant evidence for gene‐by‐sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene‐by‐sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.