Thursday, February 05, 2015

More GWAS hits for cognitive ability

More genome-wide significant associations between individual SNPs and cognitive ability from a sample of 50k individuals. See also First GWAS hits for cognitive ability.
Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Nature Molecular Psychiatry advance online publication 3 February 2015 doi: 10.1038/mp.2014.188

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer’s disease: TOMM40, APOE, ABCG1 and MEF2C.

See also Five years of GWAS discovery, and compare to progress with height SNPs.

For an overview of this subject see On the genetic architecture of intelligence and other quantitative traits.


EdMeasure said...

It's pretty hard for a non-expert to understand this. Is this real evidence for the genetic substrate of intelligence or not? A 1.2 % explanation of variance seems microscopic. How much of this is simply obvious neurological defects?

gwern said...

Interesting that they found so many more hits than Rietveld but at half the sample size (despite overlap). Is this the benefit of using cognitive tests rather than education as a proxy?

steve hsu said...

It's possible. Only time will tell.

Emil Kirkegaard said...

It's because their hits are in linkage disequilibrium. Among their 13 hits, there are only 3 non-LD, one of which is in LD with one of Rietveld et al's, so we only have 6 SNPs now, up from 4.

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