First robust genetic links to depression emerge by focusing on severity. Relevant to ME/CFS?

[Simon]

This new study has caused a stir, not so much for the findings themselves as for the approach that homed in on more severe cases.

Researchers have tried and failed before to find genes linked to depression, but now someone has done it, despite using a smaller sample (5,300 discovery phase, 3,000 validation phase) than previous unsuccessful attempts.

Sparse whole-genome sequencing identifies two loci for major depressive disorder : Nature

We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

The researchers recruited patients in China, reasoning that as depression is under-diagnosed there, only the more severe cases will be diagnosed (a view their data supported), and they also restricted the cohort to patients that were ethnically Han Chinese. Focusing on more severe cases increases the 'signal' strength and the ethnic focus reduces variablility ('noise') giving a stronger signal-to-noise ratio, making discoveries easier. (Focusing on severe cases may well also reduce noise/variability.)

An accompanying Nature News article highlighted the potential of this approach.

First robust genetic links to depression emerge : Nature News & Comment

But many in the field are excited that the markers have been unearthed at all. The results look set to end years of debate over whether sequences for such a complex disorder could be found — and Flint’s study may serve as a framework for future attempts to collect data from tens of thousands of people.

Maybe a similar approach would pay off in mecfs. And I sincerely hope researchers will be undertaking a serious search for a genetic links in mecfs in very large cohorts sooner rather than later.

 

[A.B.]

The interesting part:

The analysis yielded two genetic sequences that seemed to be linked to depression: one in a stretch of DNA that codes for an enzyme whose function is not fully understood, and the other next to the gene SIRT1, which is important for energy-producing cell structures called mitochondria. The correlations were confirmed in another set of more than 3,000 depressed men and women and over 3,000 controls.

According to the paper, the part that is not understood is in an intron of the LHPP gene, which contradicts what is said here in the article, because introns don't encode proteins.

I'm not expert so I'll leave room for others to comment on this.

 

[duncan]

An element of this study that certainly commanded my attention, is that they recruited based on severity.

If only that would be done earnestly with ME/CFS patients.