dc.contributor.author | Riveros-Mckay, F | |
dc.contributor.author | Roberts, D | |
dc.contributor.author | Di Angelantonio, E | |
dc.contributor.author | Yu, B | |
dc.contributor.author | Soranzo, N | |
dc.contributor.author | Danesh, J | |
dc.contributor.author | Selvin, E | |
dc.contributor.author | Butterworth, AS | |
dc.contributor.author | Barroso, I | |
dc.date.accessioned | 2022-01-19T11:59:47Z | |
dc.date.issued | 2021-11-09 | |
dc.date.updated | 2022-01-19T10:19:16Z | |
dc.description.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 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. | en_GB |
dc.description.sponsorship | Research England | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Consejo Nacional de Ciencia y Tecnología México | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.description.sponsorship | NIH/NHLBI | en_GB |
dc.description.sponsorship | NIH/NIDDK | en_GB |
dc.description.sponsorship | British Heart Foundation | en_GB |
dc.format.extent | db210320-db210320 | |
dc.format.medium | Print-Electronic | |
dc.identifier.citation | Vol. 71 (2), pp. 359–364 | en_GB |
dc.identifier.doi | https://doi.org/10.2337/db21-0320 | |
dc.identifier.grantnumber | WT206194 | en_GB |
dc.identifier.grantnumber | 489672 | en_GB |
dc.identifier.grantnumber | K24 HL152440 | en_GB |
dc.identifier.grantnumber | R01DK089174 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/128468 | |
dc.identifier | ORCID: 0000-0001-5800-4520 (Barroso, Inês) | |
dc.language.iso | en | en_GB |
dc.publisher | American Diabetes Association | en_GB |
dc.rights | © 2021 by the American Diabetes Association
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license. | en_GB |
dc.subject | Prevention | en_GB |
dc.subject | Human Genome | en_GB |
dc.subject | Genetics | en_GB |
dc.subject | Diabetes | en_GB |
dc.subject | Metabolic and endocrine | en_GB |
dc.title | An expanded genome-wide association study of fructosamine levels identifies RCN3 as a replicating locus and implicates FCGRT as the effector transcript | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2022-01-19T11:59:47Z | |
dc.identifier.issn | 0012-1797 | |
dc.description | This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record | en_GB |
dc.description | Data and Resource Availability:
Summary statistics from the genome-wide association analysis in INTERVAL will be available from the GWAS catalog upon publication under accession GCST90017143. | |
dc.identifier.eissn | 1939-327X | |
dc.identifier.journal | Diabetes | en_GB |
dc.relation.ispartof | Diabetes | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2021-11-04 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2021-11-08 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2022-01-19T11:55:19Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2022-01-19T12:02:24Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2021-11-09 | |