Genome-Wide Association Study of Bone Mineral Density in Premenopausal European-American Women and Replication in African-American Women

Author:

Koller Daniel L.1,Ichikawa Shoji2,Lai Dongbing1,Padgett Leah R.2,Doheny Kimberly F.3,Pugh Elizabeth3,Paschall Justin4,Hui Siu L.2,Edenberg Howard J.15,Xuei Xiaoling5,Peacock Munro2,Econs Michael J.12,Foroud Tatiana1

Affiliation:

1. Departments of Medical and Molecular Genetics (D.L.K., D.L., H.J.E., M.J.E., T.F.), Indiana University School of Medicine, Indianapolis, Indiana 46202

2. Medicine (S.I., L.R.P., S.L.H., M.P., M.J.E.), Indiana University School of Medicine, Indianapolis, Indiana 46202

3. Center for Inherited Disease Research, Johns Hopkins University School of Medicine (K.F.D., E.P.), Baltimore, Maryland 21224

4. National Institute for Biotechnology Information (J.P.), National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892

5. Biochemistry and Molecular Biology (H.J.E., X.X.), Indiana University School of Medicine, Indianapolis, Indiana 46202

Abstract

Abstract Context: Several genome-wide association studies (GWAS) have been performed to identify genes contributing to bone mineral density (BMD), typically in samples of elderly women and men. Objective: The objective of the study was to identify genes contributing to BMD in premenopausal women. Design: GWAS using the Illumina 610Quad array in premenopausal European-American (EA) women and replication of the top 50 single-nucleotide polymorphisms (SNPs) for two BMD measures in African-American (AA) women. Subjects: Subjects included 1524 premenopausal EA women aged 20–45 yr from 762 sibships and 669 AA premenopausal women aged 20–44 yr from 383 sibships. Interventions: There were no interventions. Main Outcome Measures: BMD was measured at the lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Age- and weight-adjusted BMD values were tested for association with each SNP, with P values determined by permutation. Results: SNPs in CATSPERB on chromosome 14 provided evidence of association with femoral neck BMD (rs1298989, P = 2.7 × 10−5; rs1285635, P = 3.0 × 10−5) in the EA women, and some supporting evidence was also observed with these SNPs in the AA women (rs1285635, P = 0.003). Genes identified in other BMD GWAS studies, including IBSP and ADAMTS18, were also among the most significant findings in our GWAS. Conclusions: Evidence of association to several novel loci was detected in a GWAS of premenopausal EA women, and SNPs in one of these loci also provided supporting evidence in a sample of AA women.

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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