Acute myeloid leukemia (AML) is a complex hematologic malignancy with multiple disease subgroups defined by somatic mutations and heterogeneous outcomes. Although genome-wide association studies (GWAS Show more
Acute myeloid leukemia (AML) is a complex hematologic malignancy with multiple disease subgroups defined by somatic mutations and heterogeneous outcomes. Although genome-wide association studies (GWAS) have identified a small number of common genetic variants influencing AML risk, the heritable component of this disease outside of familial susceptibility remains largely undefined. Here, we perform a meta-analysis of 4 published GWAS plus 2 new GWAS, totaling 4710 AML cases and 12 938 controls. We identify a new genome-wide significant risk locus for pan-AML at 2p23.3 (rs4665765; P = 1.35 × 10-8; EFR3B, POMC, DNMT3A, and DNAJC27), which also significantly associates with patient survival (P = 6.09 × 10-3). Our analysis also identifies 3 new genome-wide significant risk loci for disease subgroups, including AML with deletions of chromosome 5 and/or 7 at 1q23.3 (rs12078864; P = 7.0 × 10-10; DUSP23) and cytogenetically complex AML at 2q33.3 (rs12988876; P = 3.28 × 10-8; PARD3B) and 2p21 (rs79918355; P = 1.60 × 10-9; EPCAM). We also investigated loci previously associated with the risk of clonal hematopoiesis (CH) or CH of indeterminate potential and identified several variants associated with the risk of AML. Our results further inform on AML etiology and demonstrate the existence of disease subgroup specific risk loci. Show less
Over 35% of all adults in the world are currently obese and risk of obesity in racial or ethnic minority groups exist in the US, but the causes of these differences are not all known. As obesity is a Show more
Over 35% of all adults in the world are currently obese and risk of obesity in racial or ethnic minority groups exist in the US, but the causes of these differences are not all known. As obesity is a leading cause of cardiovascular disease, an improved understanding of risk factors across racial and ethnic groups may improve outcomes. The objective of this study was to determine if susceptibility to obesity is associated with genetic variation in candidate single nucleotide polymorphisms (SNPs) in African Americans and Hispanic/Latinos. We examined data from 534 African Americans and 557 Hispanic/Latinos participants from the UIC Cohort of Patients, Family and Friends. Participants were genotyped for the top 26 obesity-associated SNPs within FTO, MC4R, TUB, APOA2, APOA5, ADIPOQ, ARL15, CDH13, KNG1, LEPR, leptin, and SCG3 genes. The mean (SD) age of participants was 49±13 years, 55% were female, and mean body mass index (BMI) was 31±7.5 kg/m2. After adjusting for age and sex, we found that rs8050136 in FTO (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.1-1.8; P = 0.01) among African Americans and rs2272383 in TUB (OR 1.34, 95% CI 1.04-1.71; P = 0.02) among Hispanic/Latinos were associated with obesity. However, none of the SNPs in multivariable analysis of either AA or H/L cohorts were significant when adjusted for multiple correction. We show that candidate SNPs in the FTO and TUB genes are associated with obesity in African Americans and Hispanic/Latinos individuals respectively. While the underlying pathophysiological mechanisms by which common genetic variants cause obesity remain unclear, we have identified novel therapeutic targets across racial and ethnic groups. Show less