Английская Википедия:Genetics of obesity

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A painting of a dark haired pink cheeked obese nude young female leaning against a table. She is holding grapes and grape leaves in her left hand which cover her genitalia.

A 1680 painting by Juan Carreño de Miranda of a girl presumed to have Prader-Willi syndrome

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%, with the typical estimate at 50%. It is likely that in each person a number of genes contribute to the likelihood of developing obesity in small part, with each gene increasing or decreasing the odds marginally, and together determining how an individual responds to the environmental factors. 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. Some of these obesogenic (weight gain) or leptogenic (weight loss) genes may influence the obese individual's 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	Шаблон:OMIM	7q31.3
leptin receptor deficiency	Шаблон:OMIM	1p31
Ghrelin	605353	3p25.3
Ghrelin receptor	601898	3q26.31
prohormone convertase-1 deficiency	Шаблон:OMIM	5q15-q21
proopiomelanocortin deficiency	Шаблон:OMIM	2p23.3
melanocortin-4 receptor polymorphism (MC4R)	Шаблон:OMIM	18q22
Шаблон:Gene		7q32.3	near D7S1804
Шаблон:Gene		13q14	near D13S257
Шаблон:Gene		6q23-q25	near D6S1009, GATA184A08, D6S2436, and D6S305
Шаблон:Gene		11q24	near D11S1998, D11S4464, and D11S912
Шаблон:Gene		16p13	near ATA41E04
Шаблон:Gene		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.
Шаблон:Gene		?	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	616548	1q41	Disputed metabolic function of being either a lipase or a short-chain carboxylesterase.
CB1	114610	6q15
NPY5R	602001	4q32.2

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 play 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.

Genes protective against obesity

There are also genes that can be protective against obesity. For instance, in GPR75 variants were identified as such alleles in ~640,000 sequenced exomes which may be relevant to e.g. therapeutic strategies against obesity. Other candidate anti-obesity-related genes include ALK, TBC1D1, and SRA1.

Genetic syndromes

The term "non-syndromic obesity" is sometimes used to exclude these conditions. In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviations above normal), 7% harbor a single locus mutation.

See also

• New World syndrome
• Nutritional genomics

Related:

• Human genetic variation