Established and emerging strategies to crack the genetic code of obesity

Tremendous progress has been made in the genetic elucidation of obesity over the past two decades, driven largely by technological, methodological and organizational innovations. Current strategies for identifying obesity-predisposing loci/genes, including cytogenetics, linkage analysis, homozygosity mapping, admixture mapping, candidate gene studies, genome-wide association studies, custom genotyping arrays, whole-exome sequencing and targeted exome sequencing, have achieved differing levels of success, and the identified loci in aggregate explain only a modest fraction of the estimated heritability of obesity. This review outlines the successes and limitations of these approaches and proposes novel strategies, including the use of exceptionally large sample sizes, the study of diverse ethnic groups and deep phenotypes and the application of innovative methods and study designs, to identify the remaining obesity-predisposing genes. The use of both established and emerging strategies has the potential to crack the genetic code of obesity in the not-too-distant future. The resulting knowledge is likely to yield improvements in obesity prediction, prevention and care.