Question

) GWAS have shown that:

a) common SNPs usually have a small effect on common, complex disease risk

b) rare SNPs can have a big effect on common, complex disease risk

c) risk of common, complex diseases can be accurately predicted using common SNPs

d) genetic risk factors are not important in common, complex diseases

e) the best strategy to identify genetic risk variants in common, complex disease is whole exome sequence

Answer 1

• Common SNPs usually have a small effect on common, complex disease risk - As per the common disease/common variant (CD/CV) hypothesis, common disorders are likely influenced by genetic variation that is also common in the population. After testing the hypothesis, with GWAS, it has been observed that common alleles or SNPs do play a role in susceptibility for common and complex disease with multiple susceptibility SNPs, each with small effect sizes. So for common complex diseases the CD/CV hypothesis has been proven true, but with limited success in identifying the common SNPs specific to a disease.
• The best strategy to identify genetic risk variants in common, complex disease is whole exome sequence - Due to the limited success of GWAS in identifying SNP's that are responsible for the common complex diseases, WES has been employed in large scale studies, such as to discover genes underlying cardiovascular disorders. The results of these studies have identified rare variants that may cause common complex diseases upon studying a limited number of individuals. Much larger number of individuals are required to continue the studies.