• The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

allele

ancestry

diabetes

genetic analysis

genetic structure

genome

health risk

pathology

physiology

Article

controlled study

European

exome

gene sequence

genetic code

genetic variation

genome-wide association study

genotype

human

major clinical study

non insulin dependent diabetes mellitus

priority journal

dna mutational analysis

ethnology

Europe

genetic predisposition

genetics

genotyping technique

sample size

Alleles

Diabetes Mellitus, Type 2

DNA Mutational Analysis

Exome

Genetic Predisposition to Disease

Genetic Variation

Genome-Wide Association Study

Genotyping Techniques

Humans

Sample Size

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)