Musculoskeletal disorders have been shown to have a detrimental impact on health-related quality of life across a spectrum of age-groups. Despite the high prevalence and significant impact of musculoskeletal disorders, relatively little is known about how genes work together with the environment to cause diseases of the musculoskeletal system. Common age-related conditions that are inherited, such as osteoporosis (bone loss), sarcopenia (loss of muscle), muscle weakness, foot disorders and metabolic syndrome (insulin-related obesity) result in disability and frailty. Since these conditions are genetically determined, knowledge about their molecular underpinnings may yield important discoveries related to prevention and treatment.
Targeted Sequencing of 3 Loci Associated with BMD in the Framingham Osteoporosis Study
NIAMS R01 AR 061162
This project will perform next generation sequencing of three novel loci identified in a previous genome-wide association study meta-analysis. To identify potential causal variants, re-sequencing will be performed in targeted genomic regions in 325 individuals with the lowest extremes of BMD) from the Framingham Study. This resequencing effort will be combined with a resequencing project (442 cases and 712 controls) that is currently underway in a very limited sample of Framingham subjects through a grant supporting this work in the Cohorts for the Heart and Aging Research in Genetic Epidemiology (CHARGE) consortium. By resequencing additional subjects in the Framingham Osteoporosis Study, our total sample size of 1,379 will provide sufficient power to be able to detect low frequency and rare variants that are likely to be the ones that affect bone density phenotypes.
Genetics of Foot Disorders
NIAMS R01 AR060492
This grant will examine the heritability of specific foot disorders and conduct genome-wide association study of foot disorders and foot biomechanics in two large population-based cohorts, the Framingham Study and Johnston County Osteoarthritis Project. Meta-analyses across the known cohorts with these phenotypes will be conducted and SNP findings will be replicated in other cohorts with foot and genetic data. This is the first human genome-wide association study of foot disorders and the investigators welcome contact from others across the world interested in the genetics of foot disorders in populations.
Risk Factors for Age Related Bone Loss
NIAMS/NIA R01 AR/AG41398
This is the fourth, 5-year continuation of this project examining both genetic and lifestyle factors influencing age-related bone loss and fractures. The project involves the performance of a genome-wide association study of genes responsible for bone density and quantitative ultrasound. It also examines diet by gene interactions and the role of lean leg mass on the risk of hip fracture.
Bone Microarchitecture: The Framingham Osteoporosis Study
NIAMS NIAMS R01 AR061445-01
After performing high resolution peripheral quantitative computed tomography scans on over 2,500 Framingham Study participants, the microarchitectural indices obtained from the images will be used to perform genome wide association studies, to study risk factors for bone microarchitecture, and to determine if bone microarchitecture predicts fracture.