HbA1c in Malay (JCEM 2020)

We conducted a genome-wide association analysis to discover genetic variants associated with HbA1c using two Malay studies: the Singapore Malay Eye Study (SiMES, N=1,721 on Illumina610 array) and the Living Biobank study (N=983 on Illumina OmniExpress array and whole-exome sequenced). We performed two meta-analyses: (1) imputed both studies to 1000 Genomes Phase 3, and (2) SiMES imputed to a Malay-specific reference panel built by integrating the Living Biobank array and whole-exome data. Each variant was tested for association with HbA1c in two regression models. In the first model, we used inverse-normalised residuals after regressing out age, age2, sex, and the first two principle components to test for association with each variant to obtain P-values. The second model regressed untransformed HbA1c values with age, age2, sex, the two principle components and genetic dosage for interpretable effect size change. We then carried out fixed-effects sample-size weighted meta-analysis as implemented in METAL meta-analysis tool to combine association statistics across the two Malay studies. We reported variants with association statistics in both studies.

Supplementary tables and figures

The files below contain association summary statistics for the two meta-analyses of the Malay studies.

Each file contains the following information:

  1. CHR: chromosome
  2. POS: position (hg19)
  4. N: Total sample size
  5. EFF_ALLELE: Effect allele
  6. NONEFF_ALLELE: Other allele
  7. EFF_ALLELE_FREQ: Effect allele frequency
  8. BETA: Effect estimate from analysis of untransformed HbA1c value
  9. SEBETA: Standard error of effect estimate
  10. ZSCORE: Combined z-statistics for the variant from sample-size weighted meta-analysis
  11. P: P-value

HbA1c 1000 Genomes Phase 3 meta-analysis
HbA1c Malay reference panel meta-analysis

Please refer any queries to Dr Xueling Sim (ephsx@nus.edu.sg)