Identifying Osteoporosis Genes by Whole Genome Sequencing and functional Validation in Zebra Fish
NIAMS R01 AR072199
The proposed project will identify potential causal-variants and their targeted genes via fine-mapping on previously reported GWAS loci of osteoporosis; identifying novel rare variants and structural variations associated with osteoporosis via whole genome sequencing on 10,000 samples; as well as characterizing their biological function by CRISPR/Cas9 gene-editing zebrafish models. We will also cross-reference our findings with pharmaceutical databases to identify potential targets for osteoporosis and osteoporotic fractures therapy.
Genetics of Foot Disorders
NIAMS R01 AR060492
This grant examined the heritability of specific foot disorders and conducted a 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 were conducted and SNP findings were 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.
Novel Molecular Biomarkers of Bone Microarchitecture
NIAMS R01 AR/AG41398
Our proposed work will perform high resolution peripheral quantitative computed tomography scans in over 3,000 Framingham 3rd Generation participants to determine: 1) the role of metabolomics in age-related bone loss and fractures; and 2) to determine if clonal hematopoiesis of indeterminate potential contributes to bone density, microarchitecture and strength.
The Gut Microbiome and Bone Microarchitecture
NIAMS R01 AR061445
Emerging evidence suggests that gut microbes are pivotal in integrating environmental cues with host physiology and metabolism to influence many chronic conditions, including bone metabolism. This project will extend the provocative findings in animals that the gut microbiome influences the skeleton by conducting a study in the Framingham Study cohort and the MrOS cohort to test the central hypothesis that the gut microbiome is associated with BMD, microarchitecture and strength.
Determinants and Outcomes of Age-related Muscle Loss
NIAMS R01 AG065265
Our objective is to measure total muscle mass (via the D3-creatine dilution method) in the Framingham Heart Study (FHS) and determine its association with genetic and non-genetic risk factors, and their relation with falls, injurious falls and fractures in two large, community-based cohort of older adults.