| Title | Targeted sequencing of genome wide significant loci associated with bone mineral density (BMD) reveals significant novel and rare variants: the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) targeted sequencing study. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Hsu, Y-H, Li, G, Liu, C-T, Brody, JA, Karasik, D, Chou, W-C, Demissie, S, Nandakumar, K, Zhou, Y, Cheng, C-H, Gill, R, Gibbs, RA, Muzny, DM, Santibanez, J, Estrada, K, Rivadeneira, F, Harris, T, Gudnason, V, Uitterlinden, A, Psaty, BM, Robbins, JA, L Cupples, A, Kiel, DP |
| Journal | Hum Mol Genet |
| Date Published | 2016 Sep 11 |
| ISSN | 1460-2083 |
| Abstract | BACKGROUND: Bone mineral density (BMD) is a heritable phenotype that predicts fracture risk. We performed fine-mapping by targeted sequencing at WLS, MEF2C, ARHGAP1/F2 and JAG1 loci prioritized by eQTL and bioinformatic approaches among 56 BMD loci from our previous GWAS meta-analysis. METHODS AND RESULTS: Targeted sequencing was conducted in 1,291 Caucasians from the Framingham Heart Study (n = 925) and Cardiovascular Health Study (n = 366), including 206 women and men with extreme low femoral neck (FN) BMD. A total of 4,964 sequence variants (SNVs) were observed and 80% were rare with MAF CONCLUSIONS: Our findings suggest that protein-coding variants in selected GWAS loci did not contribute to GWAS signals. By performing targeted sequencing in GWAS loci, we identified less-common and rare non-coding SNVs associated with BMD independently from GWAS common SNPs, suggesting both common and less-common variants may associate with disease risks and phenotypes in the same loci. |
| DOI | 10.1093/hmg/ddw289 |
| Alternate Journal | Hum. Mol. Genet. |
| PubMed ID | 27616567 |
| Grant List | R01 AR057118 / AR / NIAMS NIH HHS / United States |