Intelligence is associated with important economic and healthrelated life outcomes1. Despite intelligence having substantial heritability2 (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered3 5. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 1 0-8) in 1 8 genomic loci, of which 1 5 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 1 0-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 1 0-6). Despite the well-known difference in twin-based heritability2 for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 1 0-29). These findings provide new insight into the genetic architecture of intelligence.
Suzanne Sniekers, Sven Stringer , Kyoko Watanabe, Philip R Jansen, et al.2017 Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. The Lancet doi:10.1038/ng.3869
Causes of individual differences in cognitive and mental health
The main goal of our study is to quantify and understand the role of genetic variants, the environment (including lifestyle), and their interaction on outcomes related to cognitive health. In doing so we will combine expertise of statistical genetics, medical genetics, bioinformatics and functional genomics. We are specifically interested in the following health-relevant outcomes from the U.K. Biobank data: cognitive function (incl. normal function and dementia), mental health (incl. depression, neuroticism, personality, smoking, and alcohol drinking), and brain MRI. Our research will contribute to quantifying and understanding how several risk factors (e.g. lifestyle, environment, genes), both separately and in combination, influence cognitive health as well as the comorbidities between different cognitive health outcomes. Our study will consist of a combination of methods, including: - Genome-wide association studies (GWAS) that aim to identify individual genetic variants associated with a particular outcome. - Comorbidity analyses, using e.g. meta-analytic techniques, LD score regression or BOLD-GREML methods to quantify the extent of genetic overlap between particular outcomes - Gene-set analyses (e.g. using MAGMA and INRICH tools) and bioinformatic secondary analyses to understand genetic findings in terms of their biological function - Heterogeneity analyses to determine genetic subgroups of individuals - Annotation of genetic findings using external information from e.g. expression or quantitative proteomics data - Gene-by-environment correlation and interaction analyses to quantify the relevance of the interplay between genes and environment (including lifestyle) on outcomes related to cognitive health We aim to use all available observations in the UKB that are currently released and will be released in the future, and that have been successfully genotyped and have measures of relevant outcomes.
Suzanne Sniekers, Sven Stringer , Kyoko Watanabe, Philip R Jansen, et al. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence.
|Lead investigator:||Danielle Posthuma|
|Lead institution:||VU University Amsterdam|