I got introduced to basic concepts of genetics while developed methods for estimating risk (penetrance) associated with rare high-penetrant mutations, such as those in the BRCA1/2 genes, using data from the kin-cohort design pioneered by my mentor late, Dr. Sholom Wacholder. Subsequently, I developed an interest in studying gene-environment interactions, specially in the context of epidemiologic case-control design where there is considerable potential for ganing efficiency by novel analytic strategies. I began collaborating in genome-wide association studies from its early days (2006-7) and turned my attention towards a rich set of methodological issues arising from these high throughout agnostic studies. My collaborators and I developed powerful methods for genetic association testing within biologic pathways, meta-analysis accross heterogeneous phenoypes and large-scale exploration of gene-gene and gene-envionment interactions. We also conducted foundational studies establishing mathematical framework to understand potential yield for future GWAS as a function of sample size and genetic architecture of the underlying traits. Applications of these and other methods have led to new insights to genetic basis of cancers as well as a number of other complex traits.