Genome-wide association studies of obesity and metabolic syndrome

• Published in: MOLECULAR AND CELLULAR ENDOCRINOLOGY Vol. 382; no. 1; pp. 740 - 757
• Main Authors: Fall, Tove, Ingelsson, Erik
• Format: Journal Article Publication
• Language: English
• Published: Ireland Elsevier B.V 25.01.2014
• Subjects: Adiposity - genetics; appetite; Body Mass Index; Body size (biology); Chromosome Mapping; Ethnicity - genetics; Genes; Genetics; Genome-wide association studies; Genome-Wide Association Study; Humans; Markers; Metabolic diseases; Metabolic syndrome; Metabolic Syndrome - genetics; Nucleotides; Obesity; Obesity - genetics; Polymorphism; single nucleotide polymorphism; systematic review; Waist Circumference - genetics; WHR; Obesity; Genome-wide association studies; GWAS; NCEP; MR; T2D; QTL; MeSH; eQTL; WC; Metabolic syndrome; IV; GIANT; Body mass index; MetS; Genetics; CHARGE; BMI; WHO; Genetic Investigation of ANthropometric Traits; cohorts for heart and aging research in genomic epidemiology; quantitative trait locus; National Cholesterol Education Program; Mendelian randomisation; World Health Organization; instrumental variable; waist circumference; medical subject headings; expression quantitative trait locus; type 2 diabetes; genome-wide association study; waist–hip ratio
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2012.08.018

• GWAS have greatly increased the knowledge about obesity genetics. • Common forms of obesity are polygenic with small effects sizes of each variant. • The largest genetic effects size on obesity are reported for FTO variants. • We expect large advances over the coming years regarding knowledge on gene function. Until just a few years ago, the genetic determinants of obesity and metabolic syndrome were largely unknown, with the exception of a few forms of monogenic extreme obesity. Since genome-wide association studies (GWAS) became available, large advances have been made. The first single nucleotide polymorphism robustly associated with increased body mass index (BMI) was in 2007 mapped to a gene with for the time unknown function. This gene, now known as fat mass and obesity associated (FTO) has been repeatedly replicated in several ethnicities and is affecting obesity by regulating appetite. Since the first report from a GWAS of obesity, an increasing number of markers have been shown to be associated with BMI, other measures of obesity or fat distribution and metabolic syndrome. This systematic review of obesity GWAS will summarize genome-wide significant findings for obesity and metabolic syndrome and briefly give a few suggestions of what is to be expected in the next few years.