Imputation of Exome Sequence Variants into Population- Based Samples and Blood-Cell-Trait-Associated Loci in African Americans: NHLBI GO Exome Sequencing Project

摘要: Researchers have successfully applied exome sequencing to discover causal variants in selected individuals with familial, highly penetrant disorders. We demonstrate the utility of followed by imputation for discovering low-frequency associated complex quantitative traits. performed a reference panel 761 African Americans and then imputed newly discovered into larger sample more than 13,000 association testing blood cell traits hemoglobin, hematocrit, white count, platelet count. First, we illustrate feasibility our approach demonstrating genome-wide-significant associations that are not covered conventional genotyping arrays; example, one such is between higher count an MPL c.117G>T (p.Lys39Asn) variant encoding p.Lys39Asn amino acid substitution thrombpoietin receptor gene (p = 1.5 × 10−11). Second, identified missense LCT 4 × 10−13). Third, coding might account allelic heterogeneity at several known cell-associated loci: c.754T>C (p.Tyr252His) was count; CD36 c.975T>G (p.Tyr325∗) lower α-globin locus were hemoglobin. By identifying previously reported genome-wide studies, establish powerful dissecting complex, genetically heterogeneous large population-based studies.