The Contribution of Low-Frequency and Rare Coding Variation to Susceptibility to Type 2 Diabetes.

Abstract:

PURPOSE OF REVIEW:Soon after the first genome-wide association study (GWAS) for type 2 diabetes (T2D) was published, it was hypothesized that rare and low-frequency variants might explain a substantial proportion of disease risk. Rare coding variants in particular were emphasized given their large expected role in disease. This review summarizes the extent to which recent T2D genetic studies provide evidence for or against this hypothesis. RECENT FINDINGS:Following a comprehensive study of T2D genetic architecture using three sequencing and genotyping technologies, four even larger studies have provided a yet higher resolution view of the role of rare and low-frequency coding variation in T2D susceptibility. Empirical evidence strongly suggests that common regulatory variants are the dominant contributor to T2D heritability. However, rare coding variants may nonetheless be pervasive across T2D-relevant genes. A strategy using common variants to map disease genes, and rare coding variants to link molecular gene perturbations to cellular and phenotypic effects, may be an effective means to investigate T2D pathogenesis and potential new therapies.

journal_name

Curr Diab Rep

journal_title

Current diabetes reports

authors

Flannick J

doi

10.1007/s11892-019-1142-5

subject

Has Abstract

pub_date

2019-04-08 00:00:00

pages

25

issue

5

eissn

1534-4827

issn

1539-0829

pii

10.1007/s11892-019-1142-5

journal_volume

19

pub_type

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