title: Genetic susceptibility to type 2 diabetes and obesity: from genome-wide association studies to rare variants and beyond.
abstract: During the past 7 years, genome-wide association studies have shed light on the contribution of common genomic variants to the genetic architecture of type 2 diabetes, obesity and related intermediate phenotypes. The discoveries have firmly established more than 175 genomic loci associated with these phenotypes. Despite the tight correlation between type 2 diabetes and obesity, these conditions do not appear to share a common genetic background, since they have few genetic risk loci in common. The recent genetic discoveries do however highlight specific details of the interplay between the pathogenesis of type 2 diabetes, insulin resistance and obesity. The focus is currently shifting towards investigations of data from targeted array-based genotyping and exome and genome sequencing to study the individual and combined effect of low-frequency and rare variants in metabolic disease. Here we review recent progress as regards the concepts, methodologies and derived outcomes of studies of the genetics of type 2 diabetes and obesity, and discuss avenues to be investigated in the future within this research field.
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen Ø, Denmark, niels.grarup@sund.ku.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.forename: Camilla H
authors.initials: CH
authors.lastname: Sandholt
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D009765:Obesity / Q000235:genetics*