Established and emerging strategies to crack the genetic code of obesity

Abstract

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.

Loss‐of‐function mutations in the melanocortin‐3 receptor gene confer risk for human obesity: A systematic review and meta‐analysis

“…Twin‐, family‐, and population‐based studies estimate that 40%‐75% of body mass index (BMI) variability is influenced by genetic factors . This has been confirmed by the identification of 940 polygenic loci that are associated with obesity . In addition, 79 monogenic pleiotropic syndromes with obesity have been reported in literature .…”

“…[11][12][13] This has been confirmed by the identification of 940 polygenic loci that are associated with obesity. 14,15 In addition, 79 monogenic pleiotropic syndromes with obesity have been reported in literature. 16 Eight genes in the leptin-melanocortin pathway, which modulates both appetite and energy homeostasis, have been associated with non-syndromic monogenic and oligogenic obesity.…”

ASSESSMENT OAF -243A>G POLYMORPHISM OF GLUTAMATE DECARBOXYLASE 2 GENE IN OBESE PATIENTS

“…The disease has a complex etiology involving behavioral, hormonal and genetic factors (7) . Tremendous progress has been made over the past 2 decades to elucidate the genetic impact on obesity (8) . Genome-wide scans for obesityassociated genes have repetitively detected a linkage with a locus on chromosome 10p11.22-23.…”

Genome-wide association study of morbid obesity in Han Chinese

“…According to twin, family, and adoption studies, the heritability of BMI is estimated to be around 40-70% [19][20][21][22], and approximately 27% of BMI heritability may be attributed to common single nucleotide polymorphism (SNP) in adults [23]. A review on genome-wide association studies (GWAS) has documented at least 741 BMI-or obesity-related SNPs and numerous biological pathways [24]. MO, as the extreme type of obesity, may be highly associated with the common BMI-raising variants [25,26].…”