Genomic Wide Scans for Female Osteoporosis Genes

Osteoporosis is a condition of excessive skeletal fragility which results in high risk to low trauma fractures. It is the most prevalent metabolic bone disease and is a major public health problem which may result in devastating morbidity and mortality. The most powerful, measurable determinant of fracture risk is bone mineral density (BMD). More than 60% of BMD variation is attributable to genetic factors. There are gender differences in BMD that contribute to a substantially higher fracture risk among women than men. Genetic studies demonstrate that some osteoporosis risk genes/genomic regions are gender specific. However, specific such genes contributing to female BMD and to the sex differences of BMD are largely unknown. Recent rapid progresses in SNP genotyping technology, in our knowledge about human genome diversity and linkage disequilibrium (LD) patterns in the human genome as revealed have made it feasible and timely to pursue a powerful whole genome-wide association study (GWAS) to identify genes for BMD. The major goal of this project is to perform a powerful GWAS study in a large sample of US Caucasian subjects. Gender specific effects of the genetic variants will be examined. The significant genetic variants discovered will be used to design diagnostic DNA chips for prognosis for potential health problems of osteoporosis later in life.]]>
KCOS Consent FormStudy DocumentsSubjects included in this project are unrelated random US Caucasian adults. Individuals must meet the following inclusion criteria to be eligible to participate in the study: Caucasians of European origin; Be ≥18 years of age (to ensure peak bone mass is attained); Be willing to participate in the study and attend exam for bone densitometry and blood draw. We adopted the following exclusion criteria to minimize nongenetic influence on bone mass variation so as to empirically enhance the importance of individual genetic factors for bone mass: Female subjects who are, or could be pregnant; Female subjects who have had an oophorectomy; Serious residuals from cerebral vascular disease; Diabetes mellitus, except for easily controlled, non insulin dependent diabetes mellitus; Chronic renal disease manifest by serum creatinine >1.9 mg/dl; Chronic liver disease or alcoholism; Significant chronic lung disease; Corticosteroid therapy at pharmacologic levels for more than 6 months duration; Treatment with anticonvulsant therapy for more than 6 months duration; Evidence of other metabolic or inherited bone disease such as hyper- or hypoparathyroidism, Paget's disease, osteomalacia, osteogenisis imperfecta or others; Rheumatoid arthritis or collagen disease; Recent major gastrointestinal disease (within the past year) such as peptic ulcer, malabsorption, chronic ulcerative colitis, regional enteritis, or any significant chronic diarrhea state; Significant disease of any endocrine organ that would affect BMD; Hyperthyroidism; Any neurologic or musculoskeletal condition that would be a non-genetic cause of low BMD; Any disease, treatment (e.g., bisphosphonates, evista and teraparatide), or condition that would be an apparent non-genetic cause for BMD variation. ]]>