Genetics of nonsyndromic obesity.
OBJECTIVE
Common obesity is widely regarded as a complex, multifactorial trait influenced by the 'obesogenic' environment, sedentary behavior, and genetic susceptibility contributed by common and rare genetic variants. This review describes the recent advances in understanding the role of genetics in obesity.


RESULTS
New susceptibility loci and genetic variants are being uncovered, but the collective effect is relatively small and could not explain most of the BMI heritability. Yet-to-be identified common and rare variants, epistasis, and heritable epigenetic changes may account for part of the 'missing heritability'. Evidence is emerging about the role of epigenetics in determining obesity susceptibility, mediating developmental plasticity, which confers obesity risk from early life experiences. Genetic prediction scores derived from selected genetic variants, and also differential DNA methylation levels and methylation scores, have been shown to correlate with measures of obesity and response to weight loss intervention. Genetic variants, which confer susceptibility to obesity-related morbidities like nonalcoholic fatty liver disease, were also discovered recently.


CONCLUSIONS
We can expect discovery of more rare genetic variants with the advent of whole exome and genome sequencing, and also greater understanding of epigenetic mechanisms by which environment influences genetic expression and which mediate the gene-environment interaction.
aDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore bKhoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System cSingapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Singapore.
Yung Seng
YS
Lee
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D057890:Epigenomics; D005247:Feeding Behavior; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000517:prevention & control; D010641:Phenotype; D057185:Sedentary Behavior