Single nucleotide polymorphisms in JAZF1 and BCL11A gene are nominally associated with type 2 diabetes in African-American families from the GENNID study

Abstract

Prior type 2 diabetes (T2D) genome-wide association studies (GWASs) have generated a list of well-replicated susceptibility loci in populations of European and Asian ancestry. In order to validate the trans-ethnic contribution of these GWAS SNPs, we performed a family-based association analysis of 32 selected GWAS SNPs in a cohort of 1496 African American (AA) subjects from the GENNID study. Functional roles of these SNPs were evaluated by screening cis-eQTLs in transformed lymphoblast cell lines available for a sub-group of GENNID families from Arkansas. Only three of the 32 GWAS-derived SNPs showed nominally significant association with T2D in our AA cohort. Among the replicated SNPs rs864745 in JAZF1 and rs10490072 in BCL11A gene (p= 0.006 and 0.03, respectively, after adjustment for BMI) were within the 1-lod drop support interval of T2D linkage peaks reported in these families. Genotyping of 19 Tag-SNPs in these two loci revealed no further common SNPs or haplotypes that may be a stronger predictor of T2D susceptibility than the index SNPs. Six T2D GWAS SNPs (rs6698181, rs9472138, rs730497, rs10811661, rs11037909, and rs1153188) were associated with nearby transcript expression in transformed lymphoblast cell lines of GENNID AA subjects. Thus, our study indicates a nominal role for JAZF1 and BCL11A variants in T2D susceptibility in AAs and suggested little overlap in known susceptibility to T2D between European and African derived populations when considering GWAS SNPs alone.

Quantitative candidate gene association studies of metabolic traits in Han Chinese type 2 diabetes patients

“…Genome-wide linkage analysis, GWASs, and candidate gene approaches have been used wildly to decipher the genetic basis of T2DM. Over 30 T2DM susceptibility loci with different effect sizes have been identified and replicated by genetic association studies, and several genome-wide association scans for T2DM have also been carried out recently (Rung et al, 2009;Langberg et al, 2012).…”

Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case–control study in Han Chinese

“…Furthermore, Sharma et al reported that rs9472138 was significantly associated with the expression of VEGFA in transformed lymphocytes from 82 Caucasians, and human adipose and muscle expression of VEGFA was also correlated with BMI and insulin sensitivity. 33 By similar screening cis-eQTLs in transformed lymphocytes of AfricanAmerican subjects, Langberg et al 34 found that rs9472138 was associated with nearby transcript expressions (MEA1, SLC35B2, NFKBIE), but the association between the variant and T2D was not successfully validated (P¼0.128). A recent replication study with 3388 T2D cases and 2856 controls in a Japanese population failed to repeat the association between rs9472138 and T2D (OR¼1.06, P¼0.41).…”

Genomic markers associated with insulin resistance and Type 2 Diabetes in African Americans: A review.

“…After reviewing each article based on duplication and inclusion criteria, the final number of research reports identified was 13 studies, as referenced in [7]. Landberg et al noted that three of the 32 genome-wide associated search (GWAS)-derived single nucleotide polymorphisms (SNPs) showed nominally significant association with type 2 diabetes in the AA cohort [8]. Two of the replicated SNPs were rs864745 in JAZF1 gene and rs10490072 in BCL11A gene.…”