of Work: This project seeks to develop new statistical tools and to apply existing ones in evaluating gene-environment interactions and genetic susceptibility. Work proceeded in three areas: (1) improving epidemiologic study designs, (2) devising a statistical modeling approach to enhance a data analyst's ability to detect genotype-exposure interactions, and (3) combining results from published studies to better assess the putative relationship between a vitamin D receptor polymorphism and bone density. Genotyping control subjects may not be feasible if they are reluctant to contribute tissue or have concerns about privacy with genetic information. Under the often-plausible assumption that genotype and exposure are independent in a study population, we found that study designs where controls are not genotyped can use fewer subjects than other designs to achieve the same precision in estimating exposure and genotype-exposure interactions effects. To estimate genotype effects, however, requires external data about gene prevalence. Genotype-environment interactions become difficult to detect when genes have more than two alleles in part because describing interactions requires many parameters. We have proposed a way to parameterize interactions parsimoniously that allows investigators to detect certain interactions that traditional methods would miss. Combining results from 16 studies, we found evidence that a poly-morphism in the vitamin D receptor gene was associated with about a 2.5% decline in bone mineral density.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES045002-02
Application #
6162186
Study Section
Special Emphasis Panel (BB)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Shi, Min; Umbach, David M; Weinberg, Clarice R (2015) Using parental phenotypes in case-parent studies. Front Genet 6:221
Shi, Min; Umbach, David M; Weinberg, Clarice R (2014) Disentangling pooled triad genotypes for association studies. Ann Hum Genet 78:345-56
Weinberg, Clarice R; Shi, Min; DeRoo, Lisa A et al. (2014) Asymmetry in family history implicates nonstandard genetic mechanisms: application to the genetics of breast cancer. PLoS Genet 10:e1004174
Kim, Jinsil; Stirling, Kara J; Cooper, Margaret E et al. (2013) Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study. BMC Med Genet 14:77
Shi, Min; Umbach, David M; Weinberg, Clarice R (2013) Case-sibling studies that acknowledge unstudied parents and permit the inclusion of unmatched individuals. Int J Epidemiol 42:298-307
Shi, Min; Weinberg, Clarice R (2011) How much are we missing in SNP-by-SNP analyses of genome-wide association studies? Epidemiology 22:845-7
Weinberg, Clarice R; Shi, Min; Umbach, David M (2011) A sibling-augmented case-only approach for assessing multiplicative gene-environment interactions. Am J Epidemiol 174:1183-9
Shi, Min; Umbach, David M; Weinberg, Clarice R (2011) Family-based gene-by-environment interaction studies: revelations and remedies. Epidemiology 22:400-7
Yim, Hyeon Woo; Slebos, Robbert J C; Randell, Scott H et al. (2007) Smoking is associated with increased telomerase activity in short-term cultures of human bronchial epithelial cells. Cancer Lett 246:24-33
Terry, Paul D; Umbach, David M; Taylor, Jack A (2006) APE1 genotype and risk of bladder cancer: evidence for effect modification by smoking. Int J Cancer 118:3170-3

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