Next generation sequencing approaches for complex diseases

[Luciano]

Hi everyone!

 

Considering that many GWAS studies have failed to find susceptibility genes with high penetrance, therefore not explaining most of the heritability of many diseases, which approach could be more sensitive for capturing signals of susceptibility variants to complex diseases, in your opinion: sequence exome of many unrelated affected individuals and compare to controls or sequence affected and normal individuals from familial cases and combine the results with linkage analysis...

 

Thanks!

[CharonY]

The problem with these high-dimensional approaches is that false positive discoveries go up with the number of hypotheses (here: loci) being tested. I have the feeling that without more biological information most of these non-hypothesis driven approaches are shots in the dark. Throughput alone will not give the answer.