Thanks for the useful comments, especially wrt to the clear definition of resequencing.

First, on the pedantic side, is that “resequencing” is not synonymous with second generation sequencing. Resequencing is sequencing a target genome for which you already have one or more reference sequences. Contrast this with “de novo sequencing”, which generates such a reference sequence when none is available.

Second, a key bit of information is copy number, and while it is suggestive that at least some exome sequencing approaches preserve this, they may not do so fully (i.e. introduce some distortion).

Third, it may soon be a moot point. Exome sequencing adds additional steps, whose cost is worth it if you save money on everything else. The cost of whole genome sequencing is coming down very rapidly, whereas the cost of various exome selection methods is not on such a trend. If the added cost of selection outweighs downstream efficiencies, then targeted sequencing won’t be competitive. For whole exome sequencing — barring some major improvements in the cost — that point of lost economy is probably less than 2 years away.

Thanks for you question. I’ll try to clarify a bit.

The correlation itself doesn’t support any genetic source. That’s similar to the argument concerning correlation and causation I wrote about earlier. However, correlation is a descriptive measure, and is very useful for researchers starting to dissect a disease. They want to understand everything the can about the origins and manifestation of a condition, so correlations with other diseases are part of that.

In this instance the genetic link is made because not only are the two conditions, depression and migraines (in particular migraines with aura) correlated, but because they both have a high heritability, which suggests that genetics are playing more than just a random role in the cause of both those conditions.

So, High heritability plus high odds ratios leads to the conclusion of a common genetic origin.

However, actual genetic analysis can show a much more complicated picture. For example, many genes contributing to the conditions, which may not even be the same in all individuals.

I cna be confusing, but I hope that clears some things up.

Dr. Rick