Assessment of gene-by-sex interaction effect on bone mineral density.
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 LB., Khusainova RI., Koromila T., Kung AW., Lewis JR., Masi L., Mencej-Bedrac S., Nogues X., Nogues X., Patel MS., Prezelj J., Richards JB., Sham PC., Spector T., Vandenput L., Xiao S-M., Zheng H-F., Zhu K., Balcells S., Brandi ML., Frost M., Goltzman D., González-Macías J., Karlsson M., Khusnutdinova EK., Kollia P., Langdahl BL., 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 JB., 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 JP., Psaty BM., Robbins JA., Zillikens MC., Vanduijn CM., Prince RL., Karasik D., Rivadeneira F., Kiel DP., Cupples LA., Hsu Y-H.
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