Wednesday, June 10, 2015

More GWAS hits on cognitive ability: ESHG 2015



This is a talk from ESHG 2015, which just happened in Glasgow. The abstract is old; at the talk the author reportedly described something like 70 genome wide significant hits (from an even larger combined sample) which are most likely associated with cognitive ability. This is SSGAC ... stay tuned!
Title: C15.1 - Genome-wide association study of 200,000 individuals identifies 18 genome-wide significant loci and provides biological insight into human cognitive function

Keywords: Educational attainment; genome-wide association; cognitive function

Authors: T. Esko1,2,3, on the behalf of Social Science Genetic Association Consortium (SSGAC); 1Estonian Genome Center, University of Tartu, Tartu, Estonia, 2Boston Children’s Hospital, Boston, MA, United States, 3Broad Institute of Harvard and MIT, Cambridge, MA, United States.

Abstract: Educational attainment, measured as years of schooling, is commonly used as a proxy for cognitive function. A recent genome wide association study (GWAS) of educational attainment conducted in a discovery sample of 100,000 individuals identified and replicated three genome-wide significant loci. Here, we report preliminary results based on conducted in 200,000 individuals. We replicate the previous three loci and report 15 novel, genome-wide significant loci for educational attainment. A polygenic score composed of 18 single nucleotide polymorphisms, one from each locus, explains ~0.4% of the variance educational attainment. Applying data-driven computational tools, we find that genes in loci that reach nominal significance (P < 5.0x10-5) strongly enrich for 11 groups of biological pathways (false discovery rates < 0.05) mostly related to the central nervous system, including dendritic spine morphogenesis (P=1.2x10-7), axon guidance (P=5.8x10-6) and synapse organization (P=1.7x10-5), and show enriched expression in various brain areas, including hippocampus, limbic system, cerebral and entorhinal cortex. We also prioritized genes in associated loci and found that several are known to harbor genes related to intellectual disability (SMARCA2, MAPT), obesity (RBFOX3, SLITRK5), and schizophrenia (GRIN2A) among others. By pointing at specific genes, pathways and brain areas, our work provides novel biological insights into several facets of human cognitive function.

11 comments:

ben_g said...

"Educational attainment, measured as years of schooling, is commonly used as a proxy for cognitive function."

Really high achievers have a habit of dropping out of higher education.

steve hsu said...

You just need a sufficient overall correlation between edu years and cognitive ability in order to use it to find cognitive hits. Of course some of the hits could be on something other than cognitive ability, such as Conscientiousness, but you follow up by testing your hits against samples for which you have direct cognitive measurements.

ben_g said...

How satisfied are you with the current definitions of the traits? Would you envision something like cognitive tests being replaced with more biological measures like brain physiology? Or are you happy with the definition of cognitive ability as the correlation between tests (g-factor).

gwern said...

As many as 70? Looks like we have an exciting paper to look forward to. Hopefully they'll get the preprint up soon.

Bibibibibib Blubb said...

Where is the 200 000 sample from? Do you know?

MUltan said...

Anyone who can't avoid seeing the problems with the party lines promulgated by each academic discipline, and particularly those who express those problems and don't have the capacity for doublethink academics need in order to cope with cognitive dissonance is not going to be awarded a certificate of conformity (degree). On the other hand, those who get such certificates are not going to rock the boat with original insights.

aseuss said...

Not really. For every Bill Gates, there are many more who stick with it, earn doctorates, and contribute to their respective fields. None of the winners of Turing Prizes, Nobel Prizes, or Fields Medals "dropped out" of education. And there are others who didn't win prestigious awards but nonetheless produced original ideas and insights.

aseuss said...

I do share your doubts regarding correlation of cognitive ability with tests, years of schooling, etc

Theresa Klein said...

No possible reason why some people might drop out of school other than they can't hack it, is there?

Kiki Insultcat said...

No possible way a correlation exists with outliers, is there?

Emil Kirkegaard said...

We emailed the authors to get the SNPs, but they wouldn't share them. However they wrote:
"Thanks for the interest. Our study actually now includes 300,000 samples, which resulted 74 Educational Attainment associated variants. To answer your questions – 1) our findings are submitted and being currently reviewed; and 2) I am afraid I cannot share any results. Although you could submit brief proposal to SSGAC core PIs (Benjamin, Cesarini, Koellinger) – then your project will be openly discussed among the core team, which could lead to pre-publication collaborations."

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