Osteoporotic fractures and low bone mineral density (BMD) are serious public health burdens. Substantial evidence exists that BMD is partially determined by genetics, although to date, few genes influencing variation in BMD have been identified. The majority of genetic studies have been conducted in Caucasian populations;examining the relationship between genetics and BMD in an ethnically diverse population (Mexican Americans) and a founder population (Amish) may facilitate identification of novel genetic loci associated with BMD. Our strategy is to: 1) conduct a genome wide association study (GWAS) in two populations of large, multigenerational families;2) carry out formal meta-analysis of BMD between the two populations;and 3) conduct pathway based analyses and tests of gene-by-gene interaction among genes within these biological pathways. These research objectives were developed to complement the training component of this proposal, the objectives of which are to: 1) obtain more advance training in the genetics of BMD;2) develop expertise with contemporary methods of genetic analysis employed in GWAS;and 3) gain experience with family-based genetic epidemiology studies. The goal of this study is to identify genes that influence BMD, which may provide new insights into the underlying biology and risk factors of bone disease.

Public Health Relevance

Osteoporosis contributes substantially to disability and morbidity in older populations. The objective of this study is to identify genes that influence bone mineral density in two different populations. Better understanding of the genetics of bone mineral density and osteoporosis may help develop new prevention and treatment strategies that ultimately decrease the public health burden of this disease.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Postdoctoral Individual National Research Service Award (F32)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-F16-B (20))
Program Officer
Sharrock, William J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang et al. (2017) Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun 8:80
de Vries, Paul S; Sabater-Lleal, Maria; Chasman, Daniel I et al. (2017) Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study. PLoS One 12:e0167742
Tajuddin, Salman M; Schick, Ursula M; Eicher, John D et al. (2016) Large-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases. Am J Hum Genet 99:22-39
Trégouët, D A; Delluc, A; Roche, A et al. (2016) Is there still room for additional common susceptibility alleles for venous thromboembolism? J Thromb Haemost 14:1798-802
Hardy, Shakia T; Loehr, Laura R; Butler, Kenneth R et al. (2015) Reducing the Blood Pressure-Related Burden of Cardiovascular Disease: Impact of Achievable Improvements in Blood Pressure Prevention and Control. J Am Heart Assoc 4:e002276
Appiah, Duke; Winters, Stephen J; Allison, Matthew A et al. (2015) Cardiovascular disease among women with and without diabetes mellitus and bilateral oophorectomy. Diabetes Res Clin Pract 108:473-81
Nair, Sangeeta; Slaughter, James C; Terry, James G et al. (2015) Anti-mullerian hormone (AMH) is associated with natural menopause in a population-based sample: The CARDIA Women's Study. Maturitas 81:493-8
Kemp, John P; Medina-Gomez, Carolina; Estrada, Karol et al. (2014) Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment. PLoS Genet 10:e1004423
Gorden, Alexis; Yang, Rongze; Yerges-Armstrong, Laura M et al. (2013) Genetic variation at NCAN locus is associated with inflammation and fibrosis in non-alcoholic fatty liver disease in morbid obesity. Hum Hered 75:34-43
Yerges-Armstrong, Laura M; Shen, Haiqing; Ryan, Kathleen A et al. (2013) Decreased bone mineral density in subjects carrying familial defective apolipoprotein B-100. J Clin Endocrinol Metab 98:E1999-2005

Showing the most recent 10 out of 19 publications