Dataset Information

Obesity-related loci in TMEM18, CDKAL1 and FAIM2 are associated with obesity and type 2 diabetes in Chinese Han patients.

ABSTRACT:

Background

Several obesity susceptibility loci in genes, including GNPDA2, SH2B1, TMEM18, MTCH2, CDKAL1, FAIM2, and MC4R, have been identified by genome-wide association studies. The purpose of this study was to investigate whether these loci are associated with the concurrence of obesity and type 2 diabetes in Chinese Han patients.

Methods

Using the SNaPshot technique, we genotyped seven single nucleotide polymorphisms (SNPs) in 439 Chinese patients living in Northeast China who presented at The Second Hospital of Jilin University. We analyzed the associations between these seven alleles and clinical characteristics.

Results

Risk alleles near TMEM18 (rs6548238) were associated with increased waist circumference, waist/hip ratio, body mass index (BMI), fasting plasma glucose, hemoglobin A1c, diastolic blood pressure, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol; risk alleles of CDKAL1 (rs7754840) were associated with increased waist circumference and waist/hip ratio; and FAIM2 (rs7138803) risk alleles were linked to increased BMI, diastolic blood pressure, and triglycerides (all P?ConclusionWe found that loci near TMEM18 (rs6548238), CDKAL1 (rs7754840), and FAIM2 (rs7138803) may be associated with obesity-related indicators, and loci near TMEM18 (rs6548238) and FAIM2 (rs7138803) may increase susceptibility of concurrent type 2 diabetes associated with obesity.

SUBMITTER: Kang J

PROVIDER: S-EPMC7106578 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Obesity-related loci in TMEM18, CDKAL1 and FAIM2 are associated with obesity and type 2 diabetes in Chinese Han patients.

Kang Jing J Guan Ren-Chu RC Zhao Ying Y Chen Yan Y

BMC medical genetics 20200330 1

<h4>Background</h4>Several obesity susceptibility loci in genes, including GNPDA2, SH2B1, TMEM18, MTCH2, CDKAL1, FAIM2, and MC4R, have been identified by genome-wide association studies. The purpose of this study was to investigate whether these loci are associated with the concurrence of obesity and type 2 diabetes in Chinese Han patients.<h4>Methods</h4>Using the SNaPshot technique, we genotyped seven single nucleotide polymorphisms (SNPs) in 439 Chinese patients living in Northeast China who ...[more]

PMID: 32228543

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Project description:Aims/hypothesisGenome-wide association (GWA) studies have identified hundreds of common genetic variants associated with obesity and type 2 diabetes. These studies have usually focused on additive association tests. Identifying deviations from additivity may provide new biological insights and explain some of the missing heritability for these diseases.MethodsWe performed a GWA study using a dominance deviation model for BMI, obesity (29,925 cases) and type 2 diabetes (4,040 cases) in 120,286 individuals of British ancestry from the UK Biobank study. We also investigated whether single nucleotide polymorphisms previously shown to be associated with these traits showed any enrichment for departures from additivity.ResultsKnown obesity-associated variants in FTO showed strong evidence of deviation from additivity (p DOMDEV = 3 × 10(-5)) through a recessive effect of the allele associated with higher BMI. The average BMI of individuals carrying zero, one or two BMI-raising alleles was 27.27 (95% CI 27.22, 27.31) kg/m(2), 27.54 (95% CI 27.50, 27.58) kg/m(2) and 28.07 (95% CI 28.00, 28.14) kg/m(2), respectively. A similar effect was observed in 105,643 individuals from the GIANT Consortium (p DOMDEV = 0.003; meta-analysis p DOMDEV = 1 × 10(-7)). For type 2 diabetes, we detected a recessive effect (p DOMDEV = 5 × 10(-4)) at CDKAL1. Relative to homozygous non-risk allele carriers, homozygous risk allele carriers had an OR of 1.48 (95% CI 1.32, 1.65), while the heterozygous group had an OR of 1.06 (95% CI 0.99, 1.14), a result consistent with that of a previous study. We did not identify any novel associations at genome-wide significance.Conclusions/interpretationAlthough we found no evidence of widespread non-additive genetic effects contributing to obesity and type 2 diabetes risk, we did find robust examples of recessive effects at the FTO and CDKAL1 loci.Access to research materialsSummary statistics are available at www.t2diabetesgenes.org and by request (a.r.wood@exeter.ac.uk). All underlying data are available on application from the UK Biobank.

Dataset Information

Obesity-related loci in TMEM18, CDKAL1 and FAIM2 are associated with obesity and type 2 diabetes in Chinese Han patients.

Background

Methods

Results

Publications

Obesity-related loci in TMEM18, CDKAL1 and FAIM2 are associated with obesity and type 2 diabetes in Chinese Han patients.

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