Identification of novel high-impact recessively inherited type 2 diabetes risk variants in the Greenlandic population

Aims/hypothesis In a recent study using a standard additive genetic model, we identified a TBC1D4 loss-of-function variant with a large recessive impact on risk of type 2 diabetes in Greenlanders. The aim of the current study was to identify additional genetic variation underlying type 2 diabetes us...

Full description

Saved in:

Bibliographic Details
Published in:	Diabetologia 2018-09, Vol.61 (9), p.2005-2015
Main Authors:	Grarup, Niels, Moltke, Ida, Andersen, Mette K., Bjerregaard, Peter, Larsen, Christina V. L., Dahl-Petersen, Inger K., Jørsboe, Emil, Tiwari, Hemant K., Hopkins, Scarlett E., Wiener, Howard W., Boyer, Bert B., Linneberg, Allan, Pedersen, Oluf, Jørgensen, Marit E., Albrechtsen, Anders, Hansen, Torben
Format:	Article
Language:	eng
Subjects:	Archives & records Chromosome 22 Chromosome 5 Chromosomes, Human, Pair 22 - genetics Chromosomes, Human, Pair 5 - genetics Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics Female Gene frequency Gene Frequency - genetics Genetic diversity Genetic Predisposition to Disease - genetics Genome-Wide Association Study Genomes Genotype Genotypes Glucose tolerance Greenland Human Physiology Humans Internal Medicine Male Medicine Medicine & Public Health Metabolic Diseases N-Acetylglucosaminyltransferases - genetics Phenotypes Polymorphism, Single Nucleotide - genetics Population genetics Quality control Risk factors
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Aims/hypothesis In a recent study using a standard additive genetic model, we identified a TBC1D4 loss-of-function variant with a large recessive impact on risk of type 2 diabetes in Greenlanders. The aim of the current study was to identify additional genetic variation underlying type 2 diabetes using a recessive genetic model, thereby increasing the power to detect variants with recessive effects. Methods We investigated three cohorts of Greenlanders (B99, n = 1401; IHIT, n = 3115; and BBH, n = 547), which were genotyped using Illumina MetaboChip. Of the 4674 genotyped individuals passing quality control, 4648 had phenotype data available, and type 2 diabetes association analyses were performed for 317 individuals with type 2 diabetes and 2631 participants with normal glucose tolerance. Statistical association analyses were performed using a linear mixed model. Results Using a recessive genetic model, we identified two novel loci associated with type 2 diabetes in Greenlanders, namely rs870992 in ITGA1 on chromosome 5 (OR 2.79, p = 1.8 × 10 −8 ), and rs16993330 upstream of LARGE1 on chromosome 22 (OR 3.52, p = 1.3 × 10 −7 ). The LARGE1 variant did not reach the conventional threshold for genome-wide significance ( p
ISSN:	0012-186X 1432-0428