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Download fileAn Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript
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posted on 2021-11-09, 17:53 authored by Fernando Riveros-Mckay, David Roberts, Emanuele Di Angelantonio, Bing Yu, Nicole Soranzo, John Danesh, Elizabeth Selvin, Adam S Butterworth, Inês BarrosoFructosamine 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.