Another Paper Related to Pop Strat issues for GWAS

Another study discussing pop strat issues:

Demographic history impacts stratification in polygenic scores

Points out more issues with population stratification:

We show that when population structure is recent, it cannot be fully corrected using principal components based on common variants—the standard approach—because common variants are uninformative about recent demographic history.

They further note some limitations with sibling based studies:

While sibling-based association tests are immune to stratification, the hybrid approach of ascertaining variants in a standard GWAS and then re-estimating effect sizes in siblings reduces but does not eliminate bias. 

As I've argued previously, the "immune to stratification" point is not necessarily true secondary to factors like varying ages of the siblings and selections biases of the databases. Nonetheless, if using sibling studies  "reduces but does not eliminate bias," and they are bringing the variance explained down to 2 or 3 %, then arguably they are scraping along near the null. So, far from showing that some of the variance explained is retained in sibling studies, it might suggest that there is no real genetic component found.

Finally, it's worth pointing out that despite the growing number of studies showing pop/strat issues in the UK Biobank and other such databases, no one has taken it upon themselves to reevaluate their previous, published GWAS results in light of this. It's as if they are grandfathered in.

Depression genetic study finds nothing.

This study:

Analysis of 50,000 exome-sequenced UK Biobank subjects fails to identify genes influencing probability of psychiatric referral

Speaks for itself. There is, of course, the  usual hope for the future:

  It seems unlikely that depression genetics research will produce findings that might have a substantial clinical impact until far larger samples become available.

There is simply no reason to continue believing at this point that such genetic variants will be found. They simply don't exist. There needs to be a cutoff at which point this would be acknowledged, or this shell game will never end.

Thought Experiment on Genetics and Society

I did something like this on Twitter, but will expand it here:

Let's say we live in a society where all the citizens are genetically identical (1 male and 1 female genetic code) and further that progeny, through laboratory manipulation or the like, retain the same genetic code from one generation to the next:

Will there still be a social hierarchy in such a society? Wouldn't a society require professionals and a working class. If it was along the lines of our current system, some would be doctors and some janitors and some field workers. Would those born to wealthy and well educated families have a leg up in also achieving educational and professional success? Might one also expect some homeless, some people with substance abuse problems, some people who are unhealthy? Some who turn to a life of crime? Some who would be humanitarians? Would there not eventually be wars and some way in which groups would be prejudiced towards other groups? Would people be more alike, or would they go out of their way to differentiate and be even more diverse in personality?

This is all quite obvious, isn't it? Gene hunting is not going to uncover human nature. We are human beings first. For the most part, genes simply display the costume that each of us wears. The exceptions to this fact are simply that: exceptions.  Marking people's personal traits by identifying generally unrelated genetic variations does little more than create meaningless divisions in our society and a perception of humans as genetic automatons.

"Educational Attainment" and the Wobbly Null

New study related to genetic studies of Educational Attainment:

Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses

Like a previous study, it makes the point that within family analysis significantly "attenuates" the educational attainment, in this case related to correcting for height. Here's the rub, though. In the previous study, the fact that EA was significantly diluted by within family results was somehow lauded as a demonstration along these lines: "At least there is still something, so it proves there is some genetic component to EA." This study, however seems to take the opposite approach:

The Mendelian randomization estimate using the sample of unrelated individuals implied that each 10 cm increase in height caused an increase of 0.17 (95%CI: 0.14–0.20, p-value = 8.5 × 10−26) years of education. After allowing for a family fixed effect, the Mendelian randomization estimate was greatly attenuated suggesting little evidence of a causal effect of height on education

In this case, the attenuation was taken as evidence of a null value, to demonstrate that they were able to get the pop strat out of the picture. However, if something like height has even a small effect on EA and the tiny results for genetic variants for EA after within family analysis, then it's worth asking whether there are any actual genetic variants related to someone being better or smarter in a way that allows them to get more education (c'mon, this should be obvious), or whether there are just a few physical confounders giving us the slight variance accounted for. You can't have it both ways.