Genetics of obesity
Like many other medical conditions, obesity is the result of an interplay between environmental and genetic factors. Studies have identified variants in several genes that may contribute to weight gain and body fat distribution; although, only in a few cases are genes the primary cause of obesity.
Polymorphisms in various genes controlling appetite and metabolism predispose to obesity under certain dietary conditions. The percentage of obesity that can be attributed to genetics varies widely, depending on the population examined, from 6% to 85%. As of 2006, more than 41 sites on the human genome have been linked to the development of obesity when a favorable environment is present. The involvement of genetic factors in the development of obesity is estimated to be 40–70%. Some of these obesogenic or leptogenic genes may influence obese individuals response to weight loss or weight management.
Genes
Although genetic deficiencies are currently considered rare, variations in these genes may predispose to common obesity. Many candidate genes are highly expressed in the central nervous system.Several additional loci have been identified. Also, several quantitative trait loci for BMI have been identified.
Confirmed and hypothesized associations include:
| Condition | OMIM | Locus | Notes |
| leptin deficiency | 7q31.3 | ||
| leptin receptor deficiency | 1p31 | ||
| prohormone convertase-1 deficiency | 5q15-q21 | ||
| proopiomelanocortin deficiency | 2p23.3 | ||
| melanocortin-4 receptor polymorphism | 18q22 | ||
| 7q32.3 | near D7S1804 | ||
| 13q14 | near D13S257 | ||
| 6q23-q25 | near D6S1009, GATA184A08, D6S2436, and D6S305 | ||
| 11q24 | near D11S1998, D11S4464, and D11S912 | ||
| 16p13 | near ATA41E04 | ||
| 20pter-p11.2 | near D20S482 | ||
| INSIG2 | 2q14.1 | ||
| FTO | 16q12.2 | Adults who were homozygous for a particular FTO allele weighed about 3 kilograms more and had a 1.6-fold greater rate of obesity than those who had not inherited this trait. This association disappeared, though, when those with FTO polymorphisms participated in moderately intensive physical activity equivalent to three to four hours of brisk walking. | |
| TMEM18 | 2p25.3 | ||
| GNPDA2 | 4p13 | ||
| NEGR1 | 1p31.1 | ||
| BDNF | 11p13 | ||
| KCTD15 | 19q13.12 | KCTD15 plays a role in transcriptional repression of AP-2α, which in turn, inhibits the activity of C/EBPα, an early inducer of adipogenesis. | |
| ? | Although it does not play a role in the formation of fat itself, it does determine the location on the body where this fat is stored. | ||
| SH2B1 | 16p11.2 | ||
| MTCH2 | 11p11.2 | ||
| PCSK1 | 5q15-q21 | ||
| NPC1 | 18q11-q12 | ||
| LYPLAL1 | 1q41 | Disputed metabolic function of being either a lipase or a short-chain carboxylesterase. |
Some studies have focused upon inheritance patterns without focusing upon specific genes. One study found that 80% of the offspring of two obese parents were obese, in contrast to less than 10% of the offspring of two parents who were of normal weight.
The thrifty gene hypothesis postulates that due to dietary scarcity during human evolution people are prone to obesity. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would more likely survive famine. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. This is the presumed reason that Pima Native Americans, who evolved in a desert ecosystem, developed some of the highest rates of obesity when exposed to a Western lifestyle.
Numerous studies of laboratory rodents provide strong evidence that genetics plays an important role in obesity.
The risk of obesity is determined by not only specific genotypes but also gene-gene interactions. However, there are still challenges associated with detecting gene-gene interactions for obesity.