Missing heritability, the discussion

Jan 9th, 2012 | By | Category: Genes

image from http://genes2brains2mind2me.com/2010/04/05/bigger-genetic-studies-more-missing-heritability/

There is a discussion in genomics going on right now (well, for the last few years) about the “missing heritability.” The short of it: There are traits or diseases that appear to have large genetic basis when studying populations, but so far research has been unable to find all the specific genetic variations that could account for this. There are several different hypotheses and thoughts on why this is the case, but no definitive answer.

A paper was published last week in PNAS last week, entitled “The mystery of missing heritability: Genetic interactions create phantom heritability,” that proposes one answer, genetic interactions. This is the first in a series of papers from these authors* about this, so the discussion will continue.

Later this week, I’m going to write up a ‘layman’s’ guide to this paper and the discussion, but for now I’m going to record the discussion on twitter and the blogosphere. You have the link above, that’s the paper.

*My colleague here (Mary) posted an earlier comment by Eric Lander on this subject.

*One of the first to weigh in was “GeneWatch,” a group variously described as ‘conspiracy site’, “genetic creationists’ and worse. Expectedly, they completely misread the paper and claim that the paper proves “genetic differences only play a small role in explaining why some individuals get a disease and others don’t.” This in fact is _not_ what the paper claims. In fact, a fair reading of the paper suggests that genetic differences are indeed a huge part of the explanation of that difference.

*Razib Khan gives the paper a favorable review early on. Theres some discussion there with various takes.

I think the model works out. Frankly, I wanted to check the acknowledgments, and the people listed there give me confidence that the theory here is legitimate, even if you don’t work out the equations yourself.

*Luke Justins talks about additivity and gives a defense and over at Genomes Unzipped has a shorter post .

*Twitter discussion that I’ve read so far hasn’t been as kind, but what can one say in 140 characters (which lends itself to pith and snark :) . @avsmith comments early on with a bit of snark and disagreement. @leonidkruglyak had a similar take and thinks point 4 is key in Justin’s longer post linked above and @moorejh wasn’t quite sure what was new in the discussion.

If you want to keep up on the twitter discussion, I created a list of those discussing it (among a lot of other things). If you discuss heritability (and specifically talk about the paper, I’ll add you to the list if you comment or email.

As I see more blog posts and tweets, and other discussion, I’ll post them here. And as I said, I’ll be posting a ‘layman’s guide’ later this week.

In the meantime, here is the postscript from Luke Jostin’s post that is apropos:

* There is actually a whole world of complexity here, which starts with “additive on what scale?” and ends with your crying in a corner with a sign hanging from your neck reading “NOTHING IS TRUE”. So we’ll talk about that another time

Indeed, we will :) .

And if you have a blog post discussing this paper (or missing heritability in general), please let me know and I’ll put that here.


(*word of disclosure, author 3 is a close friend :) .

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