| Literature DB >> 22692763 |
Ching-Ti Liu1, Karol Estrada, Laura M Yerges-Armstrong, Najaf Amin, Evangelos Evangelou, Guo Li, Ryan L Minster, Melanie A Carless, Candace M Kammerer, Ling Oei, Yanhua Zhou, Nerea Alonso, Zoe Dailiana, Joel Eriksson, Natalia García-Giralt, Sylvie Giroux, Lise Bjerre Husted, Rita I Khusainova, Theodora Koromila, Annie Waichee Kung, Joshua R Lewis, Laura Masi, Simona Mencej-Bedrac, Xavier Nogues, Millan S Patel, Janez Prezelj, J Brent Richards, Pak Chung Sham, Timothy Spector, Liesbeth Vandenput, Su-Mei Xiao, Hou-Feng Zheng, Kun Zhu, Susana Balcells, Maria Luisa Brandi, Morten Frost, David Goltzman, Jesús González-Macías, Magnus Karlsson, Elza K Khusnutdinova, Panagoula Kollia, Bente Lomholt Langdahl, Osten Ljunggren, Mattias Lorentzon, Janja Marc, Dan Mellström, Claes Ohlsson, José M Olmos, Stuart H Ralston, José A Riancho, François Rousseau, Roser Urreizti, Wim Van Hul, María T Zarrabeitia, Martha Castano-Betancourt, Serkalem Demissie, Elin Grundberg, Lizbeth Herrera, Tony Kwan, Carolina Medina-Gómez, Tomi Pastinen, Gunnar Sigurdsson, Gudmar Thorleifsson, Joyce Bj Vanmeurs, John Blangero, Albert Hofman, Yongmei Liu, Braxton D Mitchell, Jeffrey R O'Connell, Ben A Oostra, Jerome I Rotter, Kari Stefansson, Elizabeth A Streeten, Unnur Styrkarsdottir, Unnur Thorsteinsdottir, Frances A Tylavsky, Andre Uitterlinden, Jane A Cauley, Tamara B Harris, John Pa Ioannidis, Bruce M Psaty, John A Robbins, M Carola Zillikens, Cornelia M Vanduijn, Richard L Prince, David Karasik, Fernando Rivadeneira, Douglas P Kiel, L Adrienne Cupples, Yi-Hsiang Hsu.
Abstract
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.Entities:
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Year: 2012 PMID： 22692763 PMCID： PMC3447125 DOI： 10.1002/jbmr.1679
Source DB: PubMed Journal: J Bone Miner Res ISSN： 0884-0431 Impact factor: 6.741