An expanded genome-wide association study of fructosamine levels identifies RCN3 as a replicating locus and implicates FCGRT as the effector transcript
Riveros-Mckay, F; Roberts, D; Di Angelantonio, E; et al.Yu, B; Soranzo, N; Danesh, J; Selvin, E; Butterworth, AS; Barroso, I
Date: 9 November 2021
Article
Journal
Diabetes
Publisher
American Diabetes Association
Publisher DOI
Abstract
Fructosamine is a measure of short-term glycemic control, which has been suggested as a
useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of
diabetes. To date, a single genome-wide association study (GWAS) including 8,951 US White
and 2,712 US Black individuals without a diabetes diagnosis has been ...
Fructosamine is a measure of short-term glycemic control, which has been suggested as a
useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of
diabetes. To date, a single genome-wide association study (GWAS) including 8,951 US White
and 2,712 US Black individuals without a diabetes diagnosis has been published. Results in
Whites and Blacks yielded different association loci, near RCN3 and CNTN5, respectively.
Here we performed a GWAS on 20,731 European ancestry blood donors, and meta-analysed
our results with previous data from US White participants from The Atherosclerosis Risk in
Communities (ARIC) study (Nmeta=29,685). We identified a novel association near GCK
(rs3757840, betameta=0.0062, MAF=0.49, pmeta=3.66x10-08) and confirmed the association
near RCN3 (rs113886122, betameta=0.0134, MAF=0.17, pmeta= 5.71x10-18). Co-localization
analysis with whole blood eQTL data suggested FCGRT as the effector transcript at the RCN3
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 corrected p<0.0012). Our results broaden knowledge of
the genetic architecture of fructosamine and prioritize FCGRT for downstream functional
studies at the established RCN3 locus.
Institute of Biomedical & Clinical Science
Collections of Former Colleges
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