Document Type

Article

Publication Date

11-28-2017

Publication Title

Cell Reports

ISSN

2211-1247

Volume

21

Issue

9

First Page

2597

Last Page

2613

DOI

https://doi.org/10.1016/j.celrep.2017.11.028

PubMed ID

29186694

Abstract

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.

Creative Commons License

Creative Commons Attribution-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.

Share

COinS