Genetic Epidemiology of Obesity

Abstract

Obesity has become a global epidemic and contributes to the increasing burden of type 2 diabetes, cardiovascular disease, stroke, some types of cancer, and premature death worldwide. Obesity is highly heritable and arises from the interactions of multiple genes, environmental factors, and behavior. In this paper, the authors reviewed recent developments in genetic epidemiologic research, focusing particularly on several promising genomic regions and obesity-related genes. Gene-gene and gene-environment interactions of obesity were also discussed. Published studies were accessed through the MEDLINE database. The authors also searched the Obesity Gene Map Database (http://obesitygene.pbrc.edu/) and conducted a manual search using references cited in relevant papers. Heritabilities for obesity-related phenotypes varied from 6% to 85% among various populations. As of October 2005, 253 quantitative trait loci for obesity-related phenotypes have been localized in 61 genome-wide linkage scans, and genetic variants in 127 biologic candidate genes have been reported to be associated with obesity-related phenotypes from 426 positive findings. Gene-gene interactions were also observed in several genes, and some genes were found to influence the effect of dietary intake and physical activity on obesity-related phenotypes. Integration of genetic epidemiology with functional genomics and proteomics studies will be required to fully understand the role of genetic variants in the etiology and prevention of obesity.

Adiponectin Level and Gene Variability Are Obesity and Metabolic Syndrome Markers in a Young Population

“…The effects of the candidate gene markers could be validly evaluated after controlling for environmental factors (e.g. physical activity, diet, smoking) and ethnicity (6,55). Finally, the answer to the question of whether or not the findings from this study can be generalized to Croatian population remains uncertain because analysis was performed in a rather small group.…”

“…The increasing prevalence of obesity in the European Union and the USA is a major health concern, and it is also becoming worrying in Croatia (4) In Croatia, the prevalence of overweight, obesity and central obesity is estimated to be 38.11%, 20.34% and 43.52%, respectively (5). The genetics of obesity is complex and involves interactions between genes, gene and environment, and gene and nutrition and behavioral factors (6). Genome-wide association studies (GWAS) have identified numerous obesityrelated loci but precise identification of correlation between DNA sequence variation in specific gene and obesity phenotypes has been difficult (7).…”

Genetic variations in regulatory pathways of fatty acid and glucose metabolism are associated with obesity phenotypes: a population-based cohort study

“…6 At similar BMI levels, however, the amount of abdominal fat and associated health risk can differ significantly. A more sensitive measure is waist circumference, which gives information about the central fat distribution and is used to define abdominal obesity.…”

“…10,11 For waist, the heritability estimates range from 40 to 80%. 6 The 2005 update of the human obesity gene map reported 426 associations between candidate genes and obesity phenotypes. 8 Despite the long list of positive findings, meta-analyses showed sufficient evidence for an association with BMI or obesity for five genes only (PPARY2, FTO, MC4R, TNFa, PCSK1).…”

“…[12][13][14][15][16] The inconsistencies among individual studies can partly be explained by a lack of power to replicate the typically moderate-to-small effects of a single locus on polygenic obesity. 6,17 Currently, a limited number of cohort studies evaluated associations between genetic variation in candidate genes and waist. [18][19][20] In the last decade, it became feasible and affordable to analyze a large number of single nucleotide polymorphisms (SNPs) simultaneously.…”