Obesity

Obesity, becoming ever more common in modern societies, is often associated with serious health problems such as diabetes and heart disease. Obesity can be caused by a combination of too much food, too little exercise, and genetic susceptibility. Wikipedia Various genes are thought to affect susceptibility to obesity. The following are drawn primarily from genome wide association studies (GWAS), so are reports of variants often found in the general population that may (slightly) influence obesity predisposition. [See further below for obesity syndrome information.]

• APOA2
  • rs5082 (risk allele C) [PMID 17446329]
  • rs5085 appears not to be associated with type 2 diabetes. [PMID 19216768]
  • rs6413453 appears not to be associated with type 2 diabetes. [PMID 19216768]

• APOA5
  • rs662799 The variant known as -1131T>C, present in approximately 13% of a study population, modulates the effect of fat intake on body mass index (BMI) and obesity risk in both men and women. [PMID 17211608]

• FTO is also called the fatso gene. Wikipedia
  • rs9939609 is associated with changes in BMI and obesity beginning at age 7.
  • rs1121980 is strongly associated with early onset obesity.

• MC4R
  • rs2229616, also known as V103I, has been associated with appetite regulation, BMI (and thus obesity), and other features of metabolic syndrome. [PMID 18239646]

• NPY
  • A SNP in this gene may influence obesity. Washington Post

• SCG3 may influence the risk of obesity through possible regulation of hypothalamic neuropeptide secretion. [PMID 17094264] In one study, two SNPs affected the transcriptional activity of SCG3, and subjects with the minor allele seemed to be resistant to obesity. [1]
  • rs16964465
  • rs16964476
  • rs3764220 is also significantly associated with an obesity phenotype. [2]

• TUB - three linked SNPs influence obesity.
  • rs1528133
  • rs2272382
  • rs2272383

• Adiponectin is a hormone produced by fat cells.
  • The -11377 C > G adiponectin gene promoter variant is (i) associated with decreased serum adiponectin levels and therefore increased risk of obesity, (ii) correlated with the presence of coronary atherosclerosis, and (iii) significantly predictive of vascular events among men undergoing coronary angiography. [PMID 17334513]
  • rs1851665 (risk allele A) [PMID 20876611]
  • rs11924390
  • rs3865188 in the CDH13 gene (which encodes an adiponectin receptor) [PMID 20876611]
  • rs864265 in the ADIPOQ gene [PMID 20876611]
  • rs266717 in the ADIPOQ gene [20011104]
  • rs11924390 near the KNG1 gene [PMID 20876611]
  • rs7193788 [PMID 20887962]
  • rs6444175 [PMID 20011104]
  • rs4311394 in the ARL15 gene. The risk allele, G, is also associated with increased risk of coronary heart disease and type 2 diabetes. [PMID 20011104]

Other SNPs that affect obesity:

• rs6971091, in an uncharacterized gene on chromosome 7, is associated with more than doubled risk of obesity.

Obesity syndromes are quite different from the SNPs cited above, in which each SNP has quite modest effects. In contrast, obesity syndromes are monogenic, meaning a single gene inherited in a Mendelian fashion strongly influences the development of obesity. Syndromic forms of obesity are relatively rare, and in addition to obesity, include clinical characteristics such as intellectual disability, dysmorphic features and congenital abnormalities affecting specific organs. Examples of such syndromes are Prader-Willi and Bardet-Biedl syndrome. Non-syndromic forms of inherited obesity generally involve mutations in the leptin/melanocortin pathway, such as mutations in the leptin receptor, prohormone convertase 1, propiomelanocortin or melanocortin 4 receptor.[PMID 28346723]

Other topics related to obesity: BMI may not reflect the amount of internal fat. [3]