Thursday, November 21, 2019

Cross Ancestry Study of Schizophrenia puts out its best face (only)

I wanted to make a few quick points about this study:
Comparative genetic architectures of schizophrenia in East Asian and European populations
I tried to ask a few questions to one of the authors promoting it on Twitter, but he did not respond, so if I am incorrect about any fact, leave a comment here and I will update. Let's start with the Abstract, which is below in full:
Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.

The reason I am showing the entire abstract is to point out what it doesn't say: That the study apparently failed to replicate any of the previous significant loci for schizophrenia (as far as I can tell). The authors simply ignore this, almost as if it is expected, yet expend a lot of time trying to make lemonade out of a lemon without telling us it was a lemon, trying to justify why schizophrenia would present in the same way in different cultures, when it is presumably due to entirely different gene sets.
In my view, you would not expect any of the loci to match between the two studies because the loci are generally false positives, probably enhanced by population stratification issues that are going to be different in these two different populations. Let me go over some of the findings and why I believe they are consistent with pop/strat, false positives after the fold:

Thursday, November 7, 2019

The Intelligence Gene Shell Game

A literature review looking at GWAS for "intelligence" brings home the point I try to make regularly on this blog:
Data on 17 published intelligence GWASs (3 of which reported no associations whatsoever) were downloaded from the GWAS Catalog and analyzed in the current study. Results show a generally low rate of replication: over 87% of the 2,335 included SNPs were reported only once, and only 4 of the 17 studies included follow-up testing in a replication sample. Of these 4, none found any replicable genome-wide significant hits.