Genome-Wide Association Study (GWAS) Identifies a Significant Acute Myeloid Leukemia (AML) Susceptibility Locus Near BICRA
Abstract
Introduction: AML is the most common form of acute leukemia in adults, but hereditary predisposition to AML has been insufficiently studied. To date, investigations of AML heritability have focused on families with a clear history of AML and identified rare highly penetrant germline mutations that segregate with disease. However, the role of common polymorphisms in susceptibility to AML is not clear. We therefore conducted the first large-scale GWAS to identify risk alleles for adult de novo AML.
Methods: Whole-genome genotyping was performed on two independent American case-control sets, using Illumina Infinium Omni-1 Quad-bead arrays. GWAS quality control measures consisted of excluding samples with <94% genotyping yield or <90% European ancestry, and variants with <94% yield, differences among batches or significant (P<10-6) deviation from Hardy-Weinberg equilibrium. Phasing and imputation yielded a total of 16,058,266 autosomal variants. Association tests were performed using logistic regression including age, sex, and ten principal components as co-variates. Selected variants were genotyped in a German validation case-control set using an Agena MassARRAY System. Results were combined using METAL with fixed effects. P<5x10-8 was considered the threshold for genome-wide significance.
Results: Two separate GWASs were performed in a total of 1,183 American AML patients from the Alliance for Clinical Trials in Oncology and 2,369 population- and age-matched controls from…
How strong is the evidence?
Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 1,183 participants or records.
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