Genetics of obesity and the prediction of risk for health

Genetics of obesity and the prediction of risk for healthGo

S

OBObesity is a disorder involving an abnormal accumulation of body fat usually 20% of the individuals weightThe NIH defines obesity as a body mass index of 30 and above. 25 and above is overweightDue to an increased intake of energy-dense foods high in fat and increased sedentary nature (low-cost calorie dense food coupled with physical inactivity)

What?Obesity is a major risk factor for cardiovascular diseases, pulmonary diseases, sleep apnea, diabetes, osteoarticular diseases, cancer and psychiatric illnessesChildhood obesity can lead to early onset Diabetes type II, increased mortality rate for coronary heart disease during adulthood

ObesityEpidemic: Obesity is the most significant contributor to poor health2.1 billion obese people in 2013Outranks smoking and drinking in its deleterious effects and health costsUN targets to stop obesitys rise by 2025

1960s- Neel- Thirfty Gene Hypothesis: Genes that predispose to obesity would have had a selective advantage in populations that frequently experienced starvationThose with said genes overreact- becoming extremely obeseGenes involved in glucose and lipid metabolism have been subject to positive selection in Asian and African ethnic groups

Obesity is highly heritableHeritable estimates typically >0.70Schizophrenia 0.81Autism (0.9)Significantly higher than hypertension (0.29) and depression (0.5)Significant heritability for skinfold thickness, waist circumference and total fat distribution

Leptin- gene for obesity that helped identify many genes in the regulation of appetiteAccounts for 5% of morbid human obesity (leptin, prohormone convertase-1,pro-opiomelanocortin)Aside from pure forms, where gene defect is in appetite regulation, onset disease characterized by hyperphagia, syndromic forms. 30 different Mendelian disorders associated to obesity

Common Polygenic obesity253 quantitative-trait loci, 52 genomic regionsTCF7L2 association with diabetesMany gene associations undetermined. Of those determined, leptin-melanocortin, proinflamatory cytokines and uncoupling proteins ADRB2 PPARG

Common Polygenic obesityGAD2- glutamic acid decarboxylase gene-associated with type 2 diabates but polymorphisms in opposite direction (SNP)Visfatin pBEF1- expressed by adipocytes, increases with fatCorrelation between plasma visfatin concentration and obesityGhrelin- hormone in stomach and small intestine that functions as appetite regulator associated with obesity

Bardet-Biedl Syndrome genesThe paper examined BBS gene variants such as leptin and its receptors for associationTwelve SNPs within BBS1, 2, 4 and 6 genes were genotyped in adult and children obesity sample setsNo associations for BBS1 despite the most frequent associationBBS2, 4 and 6 were associated. BBS6 associations with metabolism function such as dyslipidaemia and hyperglycemia

EpigeneticsHeritable influence on genes that occurs without a change in the DNA sequenceInitial report of genomic imprinting, playing a role in common obesity at three different lociEpidemics might be a significant contributor to common obesity

Prader-Willi

Several fat-derived cytokines modulate the risk of metabolic syndrome associated with obesityVariation with the adiponectine gene regulates plasma level of adinopectin reporting risk for diabetes and obesityHigh adiponectine levels can cause severe obesity but has, paradoxially,metabolic protectionObesity can be metabolically neutral if there is an effective unlimited availability of small-insulin-sensitive adipocytes

Biomarkers-used for risk prediction-repeated associationCan allow design of 2 stage monitoring for obesity: subjects genotyped for predictors and serum biomarkers monitored for changes

Losing weight does not always improve health (research on bariatric patients)In Scandinavia, those who lost weight and succeeded died earlier than those who maintained and gained weightGenetic plays a role that determines fat predisposition and dysmetabolism. Unraveling genetic background associated with each stage of obesity can determine ways to manage phenomenon