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Admixture mapping of lung cancer in 1812 African-Americans.

ABSTRACT: Lung cancer continues to be the leading cause of cancer death in the USA and the best example of a cancer with undisputed evidence of environmental risk. However, a genetic contribution to lung cancer has also been demonstrated by studies of familial aggregation, family-based linkage, candidate gene studies and most recently genome-wide association studies (GWAS). The African-American population has been underrepresented in these genetic studies and has patterns of cigarette use and linkage disequilibrium that differ from patterns in other populations. Therefore, studies in African-Americans can provide complementary data to localize lung cancer susceptibility genes and explore smoking dependence-related genes. We used admixture mapping to further characterize genetic risk of lung cancer in a series of 837 African-American lung cancer cases and 975 African-American controls genotyped at 1344 ancestry informative single-nucleotide polymorphisms. Both case-only and case-control analyses were conducted using ADMIXMAP adjusted for age, sex, pack-years of smoking, family history of lung cancer, history of emphysema and study site. In case-only analyses, excess European ancestry was observed over a wide region on chromosome 1 with the largest excess seen at rs6587361 for non-small-cell lung cancer (NSCLC) (Z-score = -4.33; P = 1.5 × 10??) and for women with NSCLC (Z-score = -4.82; P = 1.4 × 10??). Excess African ancestry was also observed on chromosome 3q with a peak Z-score of 3.33 (P = 0.0009) at rs181696 among ever smokers with NSCLC. These results add to the findings from the GWAS in Caucasian populations and suggest novel regions of interest.

SUBMITTER: Schwartz AG

PROVIDER: S-EPMC3047238 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Admixture mapping of lung cancer in 1812 African-Americans.

Schwartz Ann G AG Wenzlaff Angela S AS Bock Cathryn H CH Ruterbusch Julie J JJ Chen Wei W Cote Michele L ML Artis Amanda S AS Van Dyke Alison L AL Land Susan J SJ Harris Curtis C CC Pine Sharon R SR Spitz Margaret R MR Amos Christopher I CI Levin Albert M AM McKeigue Paul M PM

Carcinogenesis 20101129 3

Lung cancer continues to be the leading cause of cancer death in the USA and the best example of a cancer with undisputed evidence of environmental risk. However, a genetic contribution to lung cancer has also been demonstrated by studies of familial aggregation, family-based linkage, candidate gene studies and most recently genome-wide association studies (GWAS). The African-American population has been underrepresented in these genetic studies and has patterns of cigarette use and linkage dise ...[more]

PMID: 21115650

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Project description:BackgroundAdmixture mapping is a powerful approach for identifying genetic variants involved in human disease that exploits the unique genomic structure in recently admixed populations. To use existing published panels of ancestry-informative markers (AIMs) for admixture mapping, markers have to be genotyped de novo for each admixed study sample and samples representing the ancestral parental populations. The increased availability of dense marker data on commercial chips has made it feasible to develop panels wherein the markers need not be predetermined.ResultsWe developed two panels of AIMs (approximately 2,000 markers each) based on the Affymetrix Genome-Wide Human SNP Array 6.0 for admixture mapping with African American samples. These two AIM panels had good map power that was higher than that of a denser panel of approximately 20,000 random markers as well as other published panels of AIMs. As a test case, we applied the panels in an admixture mapping study of hypertension in African Americans in the Washington, D.C. metropolitan area.ConclusionsDeveloping marker panels for admixture mapping from existing genome-wide genotype data offers two major advantages: (1) no de novo genotyping needs to be done, thereby saving costs, and (2) markers can be filtered for various quality measures and replacement markers (to minimize gaps) can be selected at no additional cost. Panels of carefully selected AIMs have two major advantages over panels of random markers: (1) the map power from sparser panels of AIMs is higher than that of approximately 10-fold denser panels of random markers, and (2) clusters can be labeled based on information from the parental populations. With current technology, chip-based genome-wide genotyping is less expensive than genotyping approximately 20,000 random markers. The major advantage of using random markers is the absence of ascertainment effects resulting from the process of selecting markers. The ability to develop marker panels informative for ancestry from SNP chip genotype data provides a fresh opportunity to conduct admixture mapping for disease genes in admixed populations when genome-wide association data exist or are planned.

Dataset Information

Admixture mapping of lung cancer in 1812 African-Americans.

Publications

Admixture mapping of lung cancer in 1812 African-Americans.

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