Genome-Wide Association for HbA1c in Malay Identified Deletion on SLC4A1 that Influences HbA1c Independent of Glycemia

Chai JF 1 , Kao SL 2 , Wang C 3 , Lim VJ 1 , Khor IW 2 , Dou J 3 Show all authors , Podgornaia AI 4 , Chothani S 5 , Cheng CY 6 , Sabanayagam C 6 , Wong TY 6 , van Dam RM 1 , Liu J 2 , Reilly DF 4 , Paterson AD 7 , Sim X 1

Affiliations 

  • 1 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
  • 2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
  • 3 Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  • 4 Merck Research Laboratories, Kenilworth, New Jersey
  • 5 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
  • 6 Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
  • 7 Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada
J Clin Endocrinol Metab, 2020 Dec 01;105(12).
PMID: 32936915 DOI: 10.1210/clinem/dgaa658

Abstract

CONTEXT: Glycated hemoglobin A1c (HbA1c) level is used to screen and diagnose diabetes. Genetic determinants of HbA1c can vary across populations and many of the genetic variants influencing HbA1c level were specific to populations.

OBJECTIVE: To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals.

DESIGN AND PARTICIPANTS: We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants.

RESULTS: Meta-analysis of the 1000 Genomes imputed array data identified 4 loci at genome-wide significance (P 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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