An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript

In this study, we performed a GWAS on 20,731 European-ancestry blood donors and meta-analyzed our results with previous data from U.S. White participants from the Atherosclerosis Risk in Communities (ARIC) study (Nmeta = 29,685). We identified a novel association nearGCK (rs3757840, βmeta = 0.0062; minor allele frequency [MAF] = 0.49;Pmeta = 3.66 × 10−8) and confirmed the association nearRCN3 (rs113886122, βmeta = 0.0134; MAF = 0.17;Pmeta = 5.71 × 10−18). Colocalization analysis with whole-blood expression quantitative trait loci data suggestedFCGRT as the effector transcript at theRCN3 locus. We further showed that fructosamine has low heritability (h2 = 7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (P> 0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni-correctedP< 0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritizeFCGRT for downstream functional studies at the establishedRCN3 locus.
Source: Diabetes - Category: Endocrinology Source Type: research