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Systems Genetics, Bioinformatics and Geriomics Current Research Projects

Targeted Sequencing of 3 Loci Associated with BMD in the Framingham Osteoporosis Study
NIAMS R01 AR 061162

This project is performing next generation sequencing of three novel loci identified in a previous genome-wide association study meta-analysis.  To identify potential causal variants, re-sequencing has been 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 recently completed 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

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.

Identifying Osteoporosis Genes by Whole Genome Sequencing and Functional Validation in Zebra Fish
NIAMS R01 AR072199

To overcome these challenges and get better understanding of genome wide association study findings, we proposed to utilize whole genome sequencing in large well-phenotyped populations as well as the CRISPR/Cas9 gene-editing zebrafish model to identify potential causal variants and targeted genes influencing skeletal integrity. Findings from this work may eventually lead to new diagnostics and therapeutics of osteoporosis.