2型糖尿病 z-bo 2020-09-23 351

　　Researchers from the GoT2D and T2D-GENES projects analyzed the genetic characteristics of type 2 diabetes (T2D) and found that most T2D mutation sites revolve around common mutations identified in previous GWAS studies. Achieved that there are few rare gene mutations that constitute T2D and the relative risk is small.

　　Most T2D variants are more common

　　Researchers performed whole-genome sequencing of nearly 2,700 people of European ancestry and compared the genetic patterns of individuals with or without T2D. They also analyzed the genomic protein coding regions of more than 12,900 T2D cases and controls from five different ancestral populations, and used genotyping to analyze genomic mutations in approximately 111,550 people. This study paid special attention to potential functional alleles, analyzed common and rare variants, and identified several loci that cause T2D risk in specific populations. The results showed that most T2D variant sites are around common variants identified in previous GWAS studies.

　　The article’s co-lead author, Jason Flanic, a medical and population genetics researcher at the Broad Institute and Massachusetts General Hospital, said: “There are hundreds of genetic risks for type 2 diabetes. Based on the results of this large study, people like Jason Researchers like Flannick say, "It is common to understand the genetic basis of T2D. Need to identify mutations (mainly non-genetic mutations). Coding) has invested more energy in mechanisms that affect disease risk. "

　　Rare genetic variants are less risky In order to gain insight into the genetic structure of T2D and study the potential functions of rare variants, researchers used low-coverage genome sequencing data, deep exome sequencing data, and microarray typing data. 1,326 individuals with T2D and 1,331 individuals without T2D were analyzed. All research objects are from the Nordic and Central European regions obtained through the GoT2D alliance. Researchers have detected 26.7 million SNPs, small indels or large deletions in these individuals. As a result, 126 mutations occurred in the four T2D-related loci. By analyzing GoT2D samples and genotyping another 11,645 cases and 32,769 controls in Europe, the research team expanded the variant information to 674 suspected variants at 14 sites. This includes a newly discovered locus, which was confirmed by repeated experiments on 115,000 cases and controls. The researchers examined the known T2D loci in the analysis and discovered two other rare mutations associated with T2D.

　　Researchers analyzed the data of 28,305 European cases and 51,549 controls. They were genotyped using Illumina's Exxon chip designed using T2D-GENES data. Researchers have discovered a genome-wide association of T2D at 12 known loci and 1 new locus.

　　Special gene mutations in Asian populations

　　Next, we analyzed the individual data of GoT2D and the exome sequencing data of 6,504 T2D cases and 6,436 controls. These themes come from T2D-GENES projects in Europe, South Asia, East Asia, Hispanics, and African Americans. Researchers have discovered genome-wide variants that are highly correlated with T2D among more than 3 million protein coding sequence variants. This gene variant exists in the PAX4 transcription factor and is related to the risk of T2D in East Asian populations. By analyzing the genes near the T2DGWAS locus, the researchers found that the locus near the FES gene was significantly associated with the T2D risk in South Asian populations. By analyzing the genes affected by these mutations, the researchers built a model of the genetic structure of T2D and began to analyze the signals of functional alleles that affect the risk of T2D.