CIDR: SEQUENCING SERVICES USING WHOLE GENOME SEQUENCING FOR NCI (AMOS),

Johns Hopkins University, Baltimore MD

Investigators

Abstract

Lung cancer (LC) is the third most common cancer in the U.S. with African Americans (AAs) having the highest incidence and mortality. While previous linkage, admixture, whole-exome sequencing and genome-wide association studies in European-Americans and Asian ancestry show statistically compelling effects, much of LC heritability in AAs is yet to be explained. To date, no familial lung cancer (FLC) study has been explored in AAs. Genetic Epidemiology of Lung Cancer Consortium (GELCC) is the only consortium in the U.S. that studies FLC families, but to date, the majority of data collection and analyses are of European-Americans ancestry. Examining genetic FLC risk in AAs provides complementary data to localize susceptibility loci and DNA damage response and repair pathway genes because this population has different risk alleles, effect size, linkage patterns, and tobacco related exposures than is seen in more well-characterized racial/ethnic groups. We hypothesize that germline high-penetrance variants that are rare or low-frequency in global populations are enriched in high-risk FLC families among the AAs population. This supplemental project generates high-coverage whole-genome sequencing; utilizes publicly available whole-genome sequencing data for African population controls; and utilizes a family-based study design, ensuring we will detect people who carry rare and low-frequency variants of larger effect.