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

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 U.S. White and 2,712 U.S. Black individuals wi...

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Publicado en:Diabetes Vol. 71; no. 2; pp. 359 - 365
Autores principales: Riveros-Mckay, Fernando, Roberts, David, Di Angelantonio, Emanuele, Yu, Bing, Soranzo, Nicole, Danesh, John, Selvin, Elizabeth, Butterworth, Adam S., Barroso, Inês
Formato: research tables/charts Journal Article
Publicado: American Diabetes Association Feb2022
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Feb2022
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      pub: American Diabetes Association
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        atl: An 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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          Riveros-Mckay, Fernando
          Roberts, David
          Di Angelantonio, Emanuele
          Yu, Bing
          Soranzo, Nicole
          Danesh, John
          Selvin, Elizabeth
          Butterworth, Adam S.
          Barroso, Inês
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          Calcium Binding Proteins
          Histocompatibility Antigens
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          Carbohydrates Blood
          Genes
          Female
          Diabetes Mellitus, Type 2
          Human
          Sequence Analysis
          United States
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          Prospective Studies
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          Polymorphism, Genetic
          Genetics
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          Diabetes Mellitus, Type 2 Blood
          Genome
          Diabetes Mellitus, Type 2 Epidemiology
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          Multicenter Studies
          Evaluation Research
          Validation Studies
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          Adult: 19-44 years
          Female
          Male
      ab: 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 U.S. White and 2,712 U.S. Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near RCN3 and CNTN5, respectively. 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 near GCK (rs3757840, βmeta = 0.0062; minor allele frequency [MAF] = 0.49; Pmeta = 3.66 × 10-8) and confirmed the association near RCN3 (rs113886122, βmeta = 0.0134; MAF = 0.17; Pmeta = 5.71 × 10-18). Colocalization analysis with whole-blood expression quantitative trait loci 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.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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