Genetics of Obesity Syndromes


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Using a tape measure is a simple clinical way to estimate central fatness by measuring the waist or waist-to-hip ratio. This ratio helps indicate metabolic risk and is also strongly heritable. Morbid obesity is a recognised health burden in relation to among other things obstructive sleep apnoea, hypertension and cardiovascular disease, musculoskeletal problems, diabetes, social stigma, and depression.

The difficulty of achieving and maintaining weight loss is well known. For simple obesity, the probability of attaining normal weight was one in for men and one in for women annually, decreasing to one in for men and one in for women at nine years. Some of the explanation for the difficulty in achieving and maintaining weight loss lies in the strong heritability of obesity.

It is important to understand that it is regulation of body composition itself that appears to be under genetic control. The classic adoption studies of Stunkard originally found that adopted children resembled in thinness and fatness their genetic parents whom they had never met more than the adoptive parents they had lived with. The now famous discovery that severe obesity in a child is due to defective production of the hormone leptin by the leptin gene in fat cells, with successful treatment by recombinant human leptin, launched the current era of rare genetic mutations discovery. Lack of leptin in an individual produces extreme hyperphagia, hypogonadism and reduced sympathetic tone, which are all reversed by the replacement of leptin.

This has provided valuable insight into the mechanisms controlling appetite and energy balance involved in the overall pathophysiology of obesity. Leptin stimulates expression of pro-opiomelanocortin POMC in the arcuate nucleus in the hypothalamus, which activates multiple receptors in the central nervous system CNS while inhibiting appetite-related pathways Figure 1.


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This includes POMC mutations present with adrenocorticotropic hormone ACTH -dependent cortisol deficiency; patients with this mutation have reddish hair, lack skin pigment and develop severe obesity early in life. A number of drugs that target MC4R are under development for future pharmacological treatment. Figure 1. In the search for influence of common genes on obesity, large numbers of people have to be studied; therefore, BMI is commonly used as it is easily measured in large numbers, despite the fact that percentage of fat reflects true fatness far more accurately.

It is more likely that rare genetic variants, which outnumber the common ones in the human genome the ones being studied in GWAS , actually explain more of the heritability of human obesity and can be more readily identified at the upper end of the obesity spectrum, where the major obesity increase is occurring in our strongly obesogenic environment. Obesity is sometimes part of a rare but recognised syndrome characterised by cognitive delay, dysmorphic features and organ-specific abnormalities.

These can be identified in children:. Pigeyre, Yazdi, Kaur and Meyre list 10 forms of syndromic obesity in a review of recent progress in understanding the genetic basis of obesity. Copy-number variations CNVs in the genome have also been described in association with obesity. CNVs are segments of the genome that differ in the number of diploid copies carried by healthy individuals.

Common CNVs include chromosome 10q As we detect each specific genetic defect, we may be able to tailor treatment for the patient by replacing a gene product, altering a diet or tailoring a drug specifically to improve the defect. So far, this has been achieved clinically in patients with leptin deficiency who are treated with recombinant leptin replacement. Currently, whole-exome sequencing WES of the genome of cohorts with severe obesity child or adult and those at the extremes of the BMI classification is underway.

We predict that future studies, using more accurate phenotyping, WES and more accurate physiological measures, will progressively reveal more about as yet undiscovered rare, dominant or additive genetic determinants of obesity. The identification of many factors involved in weight control has already helped shed light on the pathways and mechanisms by which obesity develops.

Novel mutations continue to be reported in severe obesity that could enable carriers of such mutations to have more specific therapy. Forensic Psychiatry. Learning Disabilities. Old Age Psychiatry. Public Health. Clinical Oncology. Clinical Radiology. Interventional Radiology. Nuclear Medicine. Cardiothoracic Surgery. Critical Care Surgery. General Surgery. Breast Surgery. Hepatobiliary Surgery.

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Is obesity in our genes? Study strengthens genetic link to body size

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Oxford Pain Management Library. Oxford Psychiatry Library. Oxford Respiratory Medicine Library. Oxford Rheumatology Library. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. 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.

The term "non-syndromic obesity" is sometimes used to exclude these conditions. From Wikipedia, the free encyclopedia.

RACGP - Genetics of obesity

European Society of Sleep Technologists. Retrieved April 6, Mar British Medical Bulletin. Advance articles 1 : — Treatment of the Obese Patient Contemporary Endocrinology. Totowa, NJ: Humana Press.

Genetic obesity syndromes.

Retrieved April 5, Br J Anaesth. Epidemiol Rev. May Diabetes Care. Archived from the original PDF on Retrieved Adrienne; Hirschhorn, Joel N. Nature Genetics.

Genetics of Obesity Syndromes Genetics of Obesity Syndromes
Genetics of Obesity Syndromes Genetics of Obesity Syndromes
Genetics of Obesity Syndromes Genetics of Obesity Syndromes
Genetics of Obesity Syndromes Genetics of Obesity Syndromes
Genetics of Obesity Syndromes Genetics of Obesity Syndromes
Genetics of Obesity Syndromes Genetics of Obesity Syndromes

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