title: Recent Progress in the Understanding of Obesity: Contributions of Genome-Wide Association Studies.
abstract: Since 2007, discovery of genetic variants associated with general obesity and fat distribution has advanced tremendously through genome-wide association studies (GWAS). Currently, the number of robustly associated loci is 190. Even though these loci explain <3 % of the variance, they have provided us a still emerging picture of genomic localization, frequency and effect size spectra, and hints of functional implications. The translation into biological knowledge has turned out to be an immense task. However, in silico enrichment analyses of genes involved in specific pathways or expressed in specific tissues have the power to suggest biological mechanisms underlying obesity. Inspired by this, we highlight genes in five loci potentially mechanistically linked to leptin-receptor trafficking and signaling in primary cilia. The clinical application of genetic knowledge as prediction, prevention, or treatment strategies is unfortunately still far from reality. Thus, despite major advances, further research is warranted to solve one of the greatest health problems in modern society.
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2.sal, 2100, Copenhagen, Denmark. metteandersen@sund.ku.dk.
authors.forename: Mette Korre
authors.initials: MK
authors.lastname: Andersen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2.sal, 2100, Copenhagen, Denmark. camilla.sandholt@sund.ku.dk.
authors.forename: Camilla Helene
authors.initials: CH
authors.lastname: Sandholt
mesh_terms: D050218:Body Fat Distribution; D015992:Body Mass Index; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control
keywords: Body mass index; Fat distribution; Functional implications; Genome-wide association study; Obesity; Primary cilia