This project seeks to develop new statistical tools and to apply existing ones in evaluating gene-environment interactions and genetic susceptibility. Work proceeded in two areas: (1) improving epidemiologic study designs, and (2) devising a statistical modeling approach to enhance our ability to detect genotype-exposure interactions. Geneticists have proposed using cases and their parents (case-parent triads) to study genetic effects on disease risk while overcoming the problem of population stratification or admixture. If a population consists of a number of distinct subpopulations that differ in baseline disease rates and in the frequency of a genetic variant, case-control studies may find associations between the variant and disease that lack etiologic import that arise simply because of the differing characteristics of the subpopulations. Case-parent triad designs can eliminate such potentially misleading associations. We are examining designs that augment case-parent triads with control-parent triads. Such designs should extend protection against admixture to studies that examine genotype and exposure jointly. 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 could miss.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES045002-03
Application #
6106654
Study Section
Special Emphasis Panel (BB)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1998
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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