Diabetic Cohort - Singapore Prospective Study - SEED - Living Biobank GWAS

Publications

Genome-Wide Association for HbA1c in Malay Identified Deletion on SLC4A1 that Influences HbA1c Independent of Glycemia.
Chai J-F, et al.
J Clin Endocrinol Metab. 2020 Dec 1;105(12):dgaa658. doi: 10.1210/clinem/dgaa658.

Cohort Profile: The Singapore Multi-Ethnic Cohort (MEC) study.
Tan KHX, et al.
Int J Epidemiol. 2018 Feb 13. doi: 10.1093/ije/dyy014

Patterns of physical activity and sedentary behavior in a representative sample of a multi-ethnic South-East Asian population: a cross-sectional study.
Win AM, et al.
BMC Public Health. 2015 Apr 1;15:318. doi: 10.1186/s12889-015-1668-7

A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.
Chen P, et al.
PLoS One. 2013 Nov 7;8(11):e79767. doi: 10.1371/journal.pone.0079767

Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.
Sim X, et al.
PLoS Genet. 2011 Apr;7(4):e1001363. doi: 10.1371/journal.pgen.1001363

Methodology of the Singapore Indian Chinese Cohort (SICC) eye study: quantifying ethnic variations in the epidemiology of eye diseases in Asians.
Lavanya R, et al.
Ophthalmic Epidemiol. 2009 Nov-Dec;16(6):325-36. doi: 10.3109/09286580903144738

Methodology of the Singapore Indian Chinese Cohort (SICC) eye study: quantifying ethnic variations in the epidemiology of eye diseases in Asians.
Lavanya R, et al.
Ophthalmic Epidemiol. 2009 Nov-Dec;16(6):325-36. doi: 10.3109/09286580903144738

Rationale and methodology for a population-based study of eye diseases in Malay people: The Singapore Malay eye study (SiMES).
Foong AW, et al.
Ophthalmic Epidemiol. 2007 Jan-Feb;14(1):25-35 doi: 10.1080/09286580600878844

Dataset phenotypes

Phase 1 analysis:

  • HbA1c
  • HbA1c adjusted for BMI

Phase 2 analysis:

  • Body mass index (BMI)
  • Serum creatinine
  • Diastolic blood pressure
  • eGFR-creat (serum creatinine)
  • HDL cholesterol
  • LDL cholesterol
  • Systolic blood pressure

Dataset subjects

Subjects Cohort Ancestry
1,790 Diabetic Cohort (DC) - Singapore Prospective Study Program (SP2), Illumina Human 1M-Duo v3 whole genome SNP genotyping chip East Asian
2,034 Diabetic Cohort (DC) - Singapore Prospective Study Program (SP2), Illumina Human610-Quad v1.0 DNA Analysis BeadChip East Asian
1,746 Singapore Chinese Eye Study East Asian (Chinese)
2,214 Singapore Malay Eye Study East Asian (Malay)
2,370 Singapore Indian Eye Study South Asian (Indian)
900 Singapore Living Biobank East Asian (Malay)
1,055 Singapore Living Biobank East Asian (Chinese)

Projects

Diabetic Cohort-Singapore Prospective Study Program (DC-SP2) Learn more >

The Diabetic Cohort (DC) is a prospective cohort that consists of 14,355 adult patients with type 2 diabetes who were recruited from various polyclinics and restructured hospitals in the period 2004 to 2010. T2D cases were selected from the Diabetic Cohort.

The Singapore Prospective Study Program (SP2) is a population-based cohort study designed to examine the pathogenesis of cardiovascular and metabolic diseases such as hypertension, dyslipidemia, obesity, and T2D in Singapore. SP2 includes 6,968 participants from one of four previous cross-sectional studies: Thyroid and Heart Study 1982–1984, National Health Survey 1992, National University of Singapore Heart Study 1993–1995 or National Health Survey 1998. Non-diabetic controls were selected from SP2.

Singapore Epidemiology of Eye Disease (SEED) Learn more >

The Singapore Epidemiology of Eye Diseases (SEED) programme aims to document the prevalence, incidence, risk factors and public health significance of eye diseases in Singapore through large-scale population-based epidemiological studies. These studies include (1) Singapore Chinese Eye Study (SCES), (2) Singapore Malay Eye Study (SiMES) and (3) Singapore Indian Eye Study (SINDI). All three studies conducted age-stratified random sampling of adults aged 40-80+ residing in the South-Western part of Singapore.

Singapore Living Biobank

Living Biobank is a collection of population-based Chinese and Malay individuals from two multi-ethnic cohorts from Singapore Public Health Studies: Multi Ethnic Cohort (MEC) and the Singapore Health 2012 (SH2012) that aims to investigate the genetic and lifestyle factors that affect the risk of developing chronic diseases such as T2D, cardiovascular outcomes, and cancer in Singapore citizens and permanent residents. The SPHS Living Biobank is a joint collaboration with the pharmaceutical company Merck, which is also one of the industry members of the AMP T2D partnership. The primary aim is to build a catalogue of low frequency and rare coding variants in East Asians, with consent for genotype-phenotype follow-up physiological experiments that would inform and prioritise plausible drug targets. All Living Biobank samples have no prior medical history of diabetes.

Experiment summary

Meta-analysis of associations for the phenotypes listed above was performed on the cohorts listed above.

Overview of analysis and results

Data were analyzed by the Analysis Team at the Accelerating Medicines Partnership Data Coordinating Center (AMP-DCC), Broad Institute, using Loamstream software and the AMP-DCC Data Analysis Pipeline. After sample quality control (see the Quality Control report, linked below), results from the cohorts listed above were combined in meta-analysis. Results are summarized below; see the Analysis Reports (links below) for full details.

One variant associated with HbA1c levels approached genome-wide significance in both the unadjusted and BMI-adjusted models: rs1046875 in the region of the FN3KRP gene, with a p-value of 8.33 × 10−8.

Two variants associated with serum creatinine levels reached genome-wide significance: rs11255087 in the region of the SFMBT2 gene, with a p-value of 1.17 × 10−10, and rs10513120 in the region of the CLSTN2 gene, with a p-value of 9.37 × 10−10.

One variant associated with BMI reached genome-wide significance: the previously known rs8050136 in the region of the FTO gene, with a p-value of 4.05 × 10−12.

Two variants associated with systolic blood pressure reached genome-wide significance: the previously known rs17115100 in the region of the CYP17A1 gene, with a p-value of 1.2 × 10−9, and rs11668428 in the region of the UQCRFS1 gene, with a p-value of 4.58 × 10−8.

Nine variants associated with HDL cholesterol levels reached genome-wide significance. The top variant was the previously known rs3764261 in the region of the CETP gene, with a p-value of 5.9 × 10−51.

Twelve variants associated with LDL cholesterol levels reached genome-wide significance. The top variant was the previously known rs7412 in the region of the APOE gene, with a p-value of 9.42 × 10−61.

No associations with diastolic blood pressure or estimated glomerular filtration rate reached genome-wide significance.

Detailed reports

Genotype Data Quality Control Report (download PDF)

AMP-DCC Phase 1 Data Analysis Report (download PDF)

AMP-DCC Phase 2 Data Analysis Report (download PDF)

Dataset ID
GWAS_DCSP2LBSEED