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Get Free AccessAbstract 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.
Yongmei Liu, Karol Estrada, Laura M. Yerges-Armstrong, Najaf Amin, Εvangelos Εvangelou, Li Guo, Ryan L. Minster, Melanie A. Carless, Candace M. Kammerer, Ling Oei, Yanhua Zhou, Nerea Alonso, Zoe Dailiana, Joel Eriksson, Natàlia Garcia‐Giralt, Sylvie Giroux, Lise B. Husted, Р. И. Хусаинова, Theodora Koromila, Annie W.C. Kung, Joshua R. Lewis, Laura Masi, Simona Mencej-Bedrač, Xavier Nogués, Millan S. Patel, Janez Preželj, J. Brent Richards, Pak C. Sham, Timothy D. Spector, Liesbeth Vandenput, Su‐Mei Xiao, Hou‐Feng Zheng, Kun Zhu, Susana Balcells, Maria Luisa Brandi, Morten Frost, David Goltzman, Jesús González-Macı́as, Magnus K. Karlsson, Э. К. Хуснутдинова, Panagoula Κollia, Bente Langdahl, Östen 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, Marı́a T. Zarrabeitia, Martha C. Castaño‐Betancourt, Serkalem Demissie, Elin Grundberg, Lizbeth Herrera, Tony Kwan, Carolina Medina‐Gómez, Tomi Pastinen, Gunnar Sigurðsson, Guðmar Þorleifsson, Joyce BJ vanMeurs, John Blangero, Albert Hofman, Yongmei Liu, Braxton D. Mitchell, Jeffrey R. O’Connell, Ben A. Oostra, Jerome I. Rotter, Kāri Stefánsson, Elizabeth A. Streeten, Unnur Styrkársdóttir, Unnur Þorsteinsdóttir, Frances A. Tylavsky, André G. Uitterlinden, Jane A. Cauley, Tamara B. Harris, John P A Ioannidis, Bruce M. Psaty, John A. Robbins, M. Carola Zillikens, C.M. vanDuijn, Richard L. Prince, David Karasik, Fernando Rivadeneira, Douglas P. Kiel, L. Adrienne Cupples, Yi‐Hsiang Hsu (2012). Assessment of gene-by-sex interaction effect on bone mineral density. , 27(10), DOI: https://doi.org/10.1002/jbmr.1679.
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Type
Article
Year
2012
Authors
90
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1002/jbmr.1679
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