ArticleJournal of human genetics2021
GWA-based pleiotropic analysis identified potential SNPs and genes related to type 2 diabetes and obesity.
Article in Journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- A genome-wide cross-trait analysis identifies shared loci and causal relationships of obesity and lipidemic traits with psoriasis.Frontiers in immunology · 2024Pooled it
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- Multipartite network analysis to identify environmental and genetic associations of metabolic syndrome in the Korean population.Scientific reports · 2024Article
- E-GWAS: an ensemble-like GWAS strategy that provides effective control over false positive rates without decreasing true positives.Genetics, selection, evolution : GSE · 2023Article
- Molecular Genetics of Abnormal Redox Homeostasis in Type 2 Diabetes Mellitus.International journal of molecular sciences · 2023Review
- JAZF1: A metabolic actor subunit of the NuA4/TIP60 chromatin modifying complex.Frontiers in cell and developmental biology · 2023Review
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- HeterozygousGenes · 2021Article
- Genome-wide association study reveals novel loci associated with feeding behavior in Pekin ducks.BMC genomics · 2021Article
- The evolutionary origins of dementia.Journal of Alzheimer's disease reportsReview
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Metabolic syndrome is a cluster of symptoms including excessive body fat and insulin resistance which may lead to obesity and type 2 diabetes (T2D). The physiological and pathological cross-talk between T2D and obesity is crucial and complex, meanwhile, the genetic connection between T2D and obesity is largely unknown. The purpose of this study is to identify pleiotropic SNPs and genes between these two associated conditions by applying genetic analysis incorporating pleiotropy and annotation (GPA) on two large genome-wide association studies (GWAS) data sets: a body mass index (BMI) data set containing 339,224 subjects and a T2D data set containing 110,452 subjects. In all, 5182 SNPs showed pleiotropy in both T2D and obesity. After further prioritization based on suggested local false discovery rates (FDR) by the GPA model, 2146 SNPs corresponding to 217 unique genes are significantly associated with both traits (FDR < 0.2), among which 187 are newly identified pleiotropic genes compare with original GWAS in individual traits. Subsequently, gene enrichment and pathway analyses highlighted several pleiotropic SNPs including rs849135 (FDR = 0.0002), rs2119812 (FDR = 0.0018), rs4506565 (FDR = 1.23E-08), rs1558902 (7.23E-10) and corresponding genes JAZF1, SYN2, TCF7L2, FTO which may play crucial rol5es in the etiology of both T2D and obesity. Additional evidences from expression data analysis of pleiotropic genes strongly supports that the pleiotropic genes including JAZF1 (p = 1.39E-05 and p = 2.13E-05), SYN2 (p = 5.49E-03 and p = 5.27E-04), CDKN2C (p = 1.99E-12 and p = 6.27E-11), RABGAP1 (p = 3.08E-03 and p = 7.46E-03), and UBE2E2 (p = 1.83E-04 and p = 8.22E-03) play crucial roles in both obesity and T2D pathogenesis. Pleiotropic analysis integrated with functional network identified several novel and causal SNPs and genes involved in both BMI and T2D which may be ignored in single GWAS.
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