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Assessment of gene-by-sex interaction effect on bone mineral density

Liu, Ching-Ti; Estrada, Karol; Yerges-Armstrong, Laura M.; Amin, Najaf; Evangelou, Evangelos; Li, Guo; Minster, Ryan L.; Carless, Melanie A.; Kammerer, Candace M. and Oei, Ling, et al. (2012) In Journal of Bone and Mineral Research 27(10). p.2051-2064
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?X?10-5) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific... (More)
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?X?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?X?10-5; female effect?=?-0.007 and p?=?3.3?X?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?X?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. (c) 2012 American Society for Bone and Mineral Research. (Less)
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keywords
GENE-BY-SEX INTERACTION, BMD, ASSOCIATION, AGING
in
Journal of Bone and Mineral Research
volume
27
issue
10
pages
2051 - 2064
publisher
AMBMR
external identifiers
  • wos:000308925800003
  • scopus:84866668118
ISSN
1523-4681
DOI
10.1002/jbmr.1679
language
English
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yes
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395cd0c9-08c6-4ee3-94bd-ba2535ce5862 (old id 3189930)
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2012-12-03 07:10:24
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@article{395cd0c9-08c6-4ee3-94bd-ba2535ce5862,
  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?&lt;?1?X?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?X?10-5; female effect?=?-0.007 and p?=?3.3?X?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?&lt;?5?X?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. (c) 2012 American Society for Bone and Mineral Research.},
  author       = {Liu, Ching-Ti and Estrada, Karol and Yerges-Armstrong, Laura M. and Amin, Najaf and Evangelou, Evangelos and Li, Guo and Minster, Ryan L. and Carless, Melanie A. and Kammerer, Candace M. and Oei, Ling and Zhou, Yanhua and Alonso, Nerea and Dailiana, Zoe and Eriksson, Joel and Garcia-Giralt, Natalia and Giroux, Sylvie and Husted, Lise Bjerre and Khusainova, Rita I. and Koromila, Theodora and Kung, Annie WaiChee and Lewis, Joshua R. and Masi, Laura and Mencej-Bedrac, Simona and Nogues, Xavier and Patel, Millan S. and Prezelj, Janez and Richards, J. Brent and Sham, Pak Chung and Spector, Timothy and Vandenput, Liesbeth and Xiao, Su-Mei and Zheng, Hou-Feng and Zhu, Kun and Balcells, Susana and Brandi, Maria Luisa and Frost, Morten and Goltzman, David and Gonzalez-Macias, Jesus and Karlsson, Magnus and Khusnutdinova, Elza K. and Kollia, Panagoula and Langdahl, Bente Lomholt and Ljunggren, Oesten and Lorentzon, Mattias and Marc, Janja and Mellstroem, Dan and Ohlsson, Claes and Olmos, Jose M. and Ralston, Stuart H. and Riancho, Jose A. and Rousseau, Francois and Urreizti, Roser and Van Hul, Wim and Zarrabeitia, Maria T. and Castano-Betancourt, Martha and Demissie, Serkalem and Grundberg, Elin and Herrera, Lizbeth and Kwan, Tony and Medina-Gomez, Carolina and Pastinen, Tomi and Sigurdsson, Gunnar and Thorleifsson, Gudmar and VanMeurs, Joyce B. J. and Blangero, John and Hofman, Albert and Liu, Yongmei and Mitchell, Braxton D. and O'Connell, Jeffrey R. and Oostra, Ben A. and Rotter, Jerome I. and Stefansson, Kari and Streeten, Elizabeth A. and Styrkarsdottir, Unnur and Thorsteinsdottir, Unnur and Tylavsky, Frances A. and Uitterlinden, Andre and Cauley, Jane A. and Harris, Tamara B. and Ioannidis, John P. A. and Psaty, Bruce M. and Robbins, John A. and Zillikens, M. Carola and VanDuijn, Cornelia M. and Prince, Richard L. and Karasik, David and Rivadeneira, Fernando and Kiel, Douglas P. and Cupples, L. Adrienne and Hsu, Yi-Hsiang},
  issn         = {1523-4681},
  keyword      = {GENE-BY-SEX INTERACTION,BMD,ASSOCIATION,AGING},
  language     = {eng},
  number       = {10},
  pages        = {2051--2064},
  publisher    = {AMBMR},
  series       = {Journal of Bone and Mineral Research},
  title        = {Assessment of gene-by-sex interaction effect on bone mineral density},
  url          = {http://dx.doi.org/10.1002/jbmr.1679},
  volume       = {27},
  year         = {2012},
}