Scholar in 86 SNPs?

 

It is good to see James Lee on the speakers list, because he told me long ago that samples of at least 100,000 would be required to link any genes with behaviour, and that he might be under-estimating the sample size required. Now he finds some interesting links with a sample of 305,000 which look very promising.

 

86 GENOMIC SITES ASSOCIATED WITH EDUCATIONAL ATTAINMENT PROVIDE INSIGHT INTO THE BIOLOGY OF COGNITIVE PERFORMANCE James J Lee 1 , (at least 200 co-authors)2

1 University of Minnesota Twin Cities, leex2293@umn.edu.

2 Social Science Genetic Association Consortium.

 

http://www.psych.umn.edu/people/profile.php?UID=leex2293

Genome-wide association studies (GWAS) have revealed much about the biological pathways responsible for phenotypic variation in many anthropometric traits and diseases. Such studies also have the potential to shed light on the developmental and mechanistic bases of behavioral traits.

Toward this end we have undertaken a GWAS of educational attainment (EA), an outcome that shows phenotypic and genetic correlations with cognitive performance, personality traits, and other psychological phenotypes. We performed a GWAS meta-analysis of ~305,000 individuals, applying a variety of methods to address quality control and potential confounding. We estimated the genetic correlations of several different traits with EA, in essence by determining whether single-nucleotide polymorphisms (SNPs) showing large statistical signals in a GWAS meta-analysis of one trait also tend to show such signals in a meta-analysis of another. We used a variety of bio-informatic tools to shed light on the biological mechanisms giving rise to variation in EA and the mediating traits afecting this outcome. We identified 86 independent SNPs associated with EA (p < 5E-8). The robust agreement between estimates of effect sizes derived from population samples and family cohorts suggests that very little of this signal is due to confounding.

We found that both cognitive performance (0.82) and intracranial volume (0.39) show substantial genetic correlations with EA. Many of the biological pathways significantly enriched by our signals are active in early development, molding features of the brain such as its overall size, morphology, and architecture of axon-dendrite connections. Genes where de novo mutations can cause intellectual disability or autism spectrum disorder also significantly enrich the loci where our GWAS signals are found. We nominate a number of biological pathways and individual genes of likely importance in the etiology of EA and mediating phenotypes such as cognitive performance.

Our results provide insight into the developmental mechanisms giving rise to individual differences in these traits and a starting point for an analysis of evolutionary change in the human lineage.