Genome Wide Association Studies (GWAS) have looked for causative or risk genes r

Question

Genome Wide Association Studies (GWAS) have looked for causative or risk genes responsible for metabolic diseases with the assumption that there will be an underlying “common disease, common variant” relationship. In addition, it has been estimated that the Heritability of obesity is between 40% and 70%**. However, the identification of genetic variants that could explain such heritability has not been possible! This is referred to as Missing Heritability! What does that mean and speculate as to the cause! Plz explain in detail :)

Explanation / Answer

Scientist Farooqi and O'Rahilly remarked that 40 to 70% of variation in body size/weight (obesity) is controlled by genetic factors and associated this trait to 'obese (OB) gene, therefore mutation in the obcauses defect in the leptin production causing obesity. Thus deleterious mutation in OB or other important gene can lead to extreme obesity and contribute to the major. However, there are other genetic variations which control the rest of the contribution and their individual effect is less. GWAS (genome-wide association studies) has made these study more effective as they can predict both major and minor effect variations. GWAS provides a complete view on the single nucleotide polymorphisms (SNPs) variation by comparing a data set of group of individual with contrast phenotype. Recently, a GWAS study conducted for obesity, revealed only 2–4% of variability relating genetic variations with small phenotypic variation. Apart from that, there were several more variation, which were un-explained. Thus, the variability, which are unexplained and need to be associated to the trait called as missing variations A researcher Frank found 75 such variants by GWAS approach associated with obesity. These results, there is a strong interference of environmental factor for obesity, such as culture and food habit of individuals. For instance, many researcher together did and meta-analysis with nearly 40,000 individual identifies some susceptible genes, which are under strong effect of physical activity of individual (person which are more physically active have less change for disease susceptibility

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