With diverse research experience in ecology and genetics, the candidate will strive to become an independent and prominent genetic epidemiologist in area of osteoporosis research. Utilizing skills in statistical genetics, the candidate proposes to develop approaches in molecular and genetic epidemiology to search for genes underlying complex traits and to study genotype-by-environment (GXE) interaction. Osteoporotic fractures (OF) are a major public health problem associated with aging. Bone mineral density (BMD) is one major risk factor for OF. Multiple environmental and genetic factors underlie BMD variation and OF risk. Recent studies revealed several genes of potential importance for BMD with little consensus. Few studies investigated the interaction between genetic and environmental factors in determining BMD. Plans are proposed to: 1) investigate the importance of several significant genes in determining the susceptibilities to OF and BMD variation; 2) investigate the differential susceptibilities to deleterious smoking effects on bone for people of different genotypes (GXE interaction). We will recruit 1) 400 random healthy subjects (with smokers and nonsmokers, age 25-50) for a BMD study; 2) 800 random healthy subjects age 60-75, 400 with and 400 without OF, with both groups having smokers and nonsmokers; 3) genotype these subjects with RFLP and microsatellite markers; 4) analyze phenotype and molecular data by adjusting for covariates important for BMD variation and OF. Characterizing environmental and genetic factors and their interactions for BMD and OF is said to be essential for developing effective preventive interventions of OF. The research plan is well written and well conceived. The many strengths of the previous applications remain. In the last submission, the reviewers highlighted three weaknesses, which have been addressed in detail in the Introduction to Revised Application section. There are only a few remaining minor concerns. Five years of support are recommended with an outstanding level of enthusiasm.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AR002170-04
Application #
6779830
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Mcgowan, Joan A
Project Start
2001-07-01
Project End
2006-03-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$121,230
Indirect Cost
Name
Creighton University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053309332
City
Omaha
State
NE
Country
United States
Zip Code
68178
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Liu, Pengyuan; Lu, Yan; Recker, Robert R et al. (2010) ALOX12 gene is associated with the onset of natural menopause in white women. Menopause 17:152-6
Chen, Xiang-Ding; Xiao, Peng; Lei, Shu-Feng et al. (2010) Gene expression profiling in monocytes and SNP association suggest the importance of the STAT1 gene for osteoporosis in both Chinese and Caucasians. J Bone Miner Res 25:339-55
Liu, Pengyuan; Lu, Yan; Recker, Robert R et al. (2010) Association analyses suggest multiple interaction effects of the methylenetetrahydrofolate reductase polymorphisms on timing of menarche and natural menopause in white women. Menopause 17:185-90
Lu, Yan; Liu, Pengyuan; Recker, Robert R et al. (2010) TNFRSF11A and TNFSF11 are associated with age at menarche and natural menopause in white women. Menopause 17:1048-54
Zhang, Zhi-Xin; Lei, Shu-Feng; Deng, Fei-Yan et al. (2009) Bivariate genome-wide linkage analysis for traits BMD and AAM: effect of menopause on linkage signals. Maturitas 62:16-20
He, Li-Na; Recker, Robert R; Deng, Hong-Wen et al. (2009) A polymorphism of apolipoprotein E (APOE) gene is associated with age at natural menopause in Caucasian females. Maturitas 62:37-41
Lei, Shu-Feng; Wu, Shan; Li, Li-Ming et al. (2009) An in vivo genome wide gene expression study of circulating monocytes suggested GBP1, STAT1 and CXCL10 as novel risk genes for the differentiation of peak bone mass. Bone 44:1010-4
Yan, H; Liu, Y-J; Zhou, Q et al. (2009) Comparison of whole genome linkage scans in premenopausal and postmenopausal women: no bone-loss-specific QTLs were implicated. Osteoporos Int 20:771-7
Chen, Yuan; Shen, Hui; Yang, Fang et al. (2009) Choice of study phenotype in osteoporosis genetic research. J Bone Miner Metab 27:121-6

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