Genotype Imputation and Ancestry Adjustment in Cancer GWAS

The genotype data used in this project was derived from multiple GWAS studies of cancer and other phenotypes in the MEC. For all projects, Illumina Infinium arrays were used, with imputation conducted using Minimac4 and the 1000 Genomes (1000G) Project reference panel (Phase 3 v5). Both subject call rates and variant call rates were ≥ 0.95. Ethnic-specific frequencies were calculated and compared to corresponding ethnic groups in Phase3 1000G for quality control. Infoscore filtering was not implemented in an effort to include all 269 PCa-associated variants (20 (link)), as poor imputation is only likely to introduce non-differential bias. Average r² was 0.88 and only 2 SNPs (0.7%) had r² below 0.30. Principal components were calculated using EIGENSTRAT (25 (link)) with 20,202 independent common variants to adjust for potential confounding due to genetic ancestry.

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Chou A., Darst B.F., Wilkens L.R., Le Marchand L., Lilja H., Conti D.V, & Haiman C.A. (2022). Association of Prostate-Specific Antigen Levels with Prostate Cancer Risk in a Multiethnic Population: Stability over Time and Comparison with Polygenic Risk Score. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 31(12), 2199-2207.

Publication 2022

Infinium arrays

Cancer Ethnic groups Genomes Genotype Gwas Phenotypes Snps

Corresponding Organization : University of Southern California

Other organizations : Cancer Center of Hawaii, University of Hawaiʻi at Mānoa, University of Hawaii System, Memorial Sloan Kettering Cancer Center, Lund University

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Variable analysis

independent variables

Genotype data
Imputation using Minimac4 and the 1000 Genomes (1000G) Project reference panel (Phase 3 v5)

dependent variables

Cancer and other phenotypes in the MEC

control variables

Subject call rates ≥ 0.95
Variant call rates ≥ 0.95
Ethnic-specific frequencies compared to corresponding ethnic groups in Phase3 1000G for quality control
Principal components calculated using EIGENSTRAT (25) with 20,202 independent common variants to adjust for potential confounding due to genetic ancestry

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