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Assessment of gene-by-sex interaction effect on bone mineral density.
Monday,2013-01-14 17:02 America/Los_Angeles — poolea2
| Title | Assessment of gene-by-sex interaction effect on bone mineral density. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Liu, C-T, Estrada, K, Yerges-Armstrong, LM, Amin, N, Evangelou, E, Li, G, Minster, RL, Carless, MA, Kammerer, CM, Oei, L, Zhou, Y, Alonso, N, Dailiana, Z, Eriksson, J, García-Giralt, N, Giroux, S, Husted, LBjerre, Khusainova, RI, Koromila, T, Kung, AWaichee, Lewis, JR, Masi, L, Mencej-Bedrac, S, Nogues, X, Patel, MS, Prezelj, J, J Richards, B, Sham, PChung, Spector, T, Vandenput, L, Xiao, S-M, Zheng, H-F, Zhu, K, Balcells, S, Brandi, MLuisa, Frost, M, Goltzman, D, González-Macías, J, Karlsson, M, Khusnutdinova, EK, Kollia, P, Langdahl, BLomholt, Ljunggren, O, Lorentzon, M, Marc, J, Mellström, D, Ohlsson, C, Olmos, JM, Ralston, SH, Riancho, JA, Rousseau, F, Urreizti, R, Van Hul, W, Zarrabeitia, MT, Castano-Betancourt, M, Demissie, S, Grundberg, E, Herrera, L, Kwan, T, Medina-Gómez, C, Pastinen, T, Sigurdsson, G, Thorleifsson, G, Vanmeurs, JBj, Blangero, J, Hofman, A, Liu, Y, Mitchell, BD, O'Connell, JR, Oostra, BA, Rotter, JI, Stefansson, K, Streeten, EA, Styrkarsdottir, U, Thorsteinsdottir, U, Tylavsky, FA, Uitterlinden, A, Cauley, JA, Harris, TB, Ioannidis, JPa, Psaty, BM, Robbins, JA, Zillikens, CM, Vanduijn, CM, Prince, RL, Karasik, D, Rivadeneira, F, Kiel, DP, Cupples, AL, Hsu, Y-H |
| Journal | J Bone Miner Res |
| Volume | 27 |
| Issue | 10 |
| Pagination | 2051-64 |
| Date Published | 2012 Oct |
| ISSN | 1523-4681 |
| Keywords | Bone Density, Cohort Studies, Female, Genes, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Sex Characteristics |
| Abstract | <p>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.</p> |
| DOI | 10.1002/jbmr.1679 |
| Alternate Journal | J. Bone Miner. Res. |
| PubMed ID | 22692763 |
| PubMed Central ID | PMC3447125 |
| Grant List | N01 HC085086 / HC / NHLBI NIH HHS / United States R01 AR046838 / AR / NIAMS NIH HHS / United States N1AG62101A / AG / NIA NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States R01-MH-078111 / MH / NIMH NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States R01-MH-083824 / MH / NIMH NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N02 HL64278 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States R01 MH078111 / MH / NIMH NIH HHS / United States R01 AR041398 / AR / NIAMS NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States R01 AR043351 / AR / NIAMS NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States U01 HL084756 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States P30 DK072488 / DK / NIDDK NIH HHS / United States N01 HC055222 / HC / NHLBI NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States P01-HL45522 / HL / NHLBI NIH HHS / United States P01 HL045522 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States R37 MH059490 / MH / NIMH NIH HHS / United States R01 MH083824 / MH / NIMH NIH HHS / United States R01 AR43351 / AR / NIAMS NIH HHS / United States R21 AR056405 / AR / NIAMS NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States F32 AR059469 / AR / NIAMS NIH HHS / United States R01 AR050066 / AR / NIAMS NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R01 AG018728 / AG / NIA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States R01 HL088119 / HL / NHLBI NIH HHS / United States |