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Please use this identifier to cite or link to this item: http://repositorio.insp.mx:8080/jspui/handle/20.500.12096/7826
Title: Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
Keywords: AnimalsCase-Control StudiesDecision Support TechniquesDiabetes Mellitus, Type 2 genetics,Exome genetics,FemaleGene FrequencyGenome-Wide Association StudyHumansMaleMiceMice, KnockoutWhole Exome Sequencing,SD
Issue Date: 2019
Publisher: ESPM INSP
Abstract: Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10-3) and candidate genes from knockout mice (P = 5.2 × 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.
URI: sicabi.insp.mx:2019-None
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699738/pdf/collins-1536336.pdf
https://www.doi.org/10.1038/s41586-019-1231-2
http://repositorio.insp.mx:8080/jspui/handle/20.500.12096/7826
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