Contribution of Copy Number Variations to Education, Socioeconomic Status and Cognition from a Genome-Wide Study of 305,401 Subjects
Xin-Rui Wu1
1Huashan Hospital, Fudan University
Objective:
To investigate how genome-wide copy number variations (CNVs) contribute to cognition, as well as how these relevant CNVs link to health outcomes.
Background:
Educational attainment (EA), socioeconomic status (SES) and cognition are important predictors of various health outcomes, and share genetic overlaps with human diseases and traits. While part of the genetic component of EA/SES/cognition has been determined by previous genome-wide association studies, the contribution of CNV, another major source of genome structural variants, to EA/SES/cognition remains unclear.
Design/Methods:

The phenotypic indicators included: (1) EduYears and EduAge for EA, (2) household income and Townsend deprivation index (TDI) for SES and (3) seven cognitive tests. Genome-wide CNV-level and gene-level association analysis was performed by PLINK. For the identified genes, protein-protein interaction network and biological knowledgebases were utilized to decipher their functions. Finally, a phenome-wide association study was performed for each significant CNV to clarify their clinical phenotypic profiles and impact on brain structure.

Results:

Using a large-scale (n = 305,401) genome-wide CNV-level association analysis, we discovered 33 CNV loci significantly associated with EA/SES/cognition, 20 of which were novel (deletions at 2p22.2, 2p16.2, 2p12, 3p25.3, 4p15.2, 5p15.33, 5q21.1, 8p21.3, 9p21.1, 11p14.3, 13q12.13, 17q21.31 and 20q13.33, as well as duplications at 3q12.2, 3q23, 7p22.3, 8p23.1, 8p23.2, 17q12 (105 kb) and 19q13.32). The genes identified in gene-level tests were enriched in biological pathways such as neurodegeneration, telomere maintenance and axon guidance. Phenome-wide association studies further identified novel associations of EA/SES/cognition-associated CNVs with mental and physical diseases, such as 6q27 duplication with upper respiratory disease and 17q12 (105 kb) duplication with mood disorders.

Conclusions:
Our findings provide a genome-wide CNV profile for EA/SES/cognition and bridge their connections to health. The expanded candidate CNVs database and the residing genes would be a valuable resource for future studies aimed at uncovering the biological mechanisms underlying cognitive function and related clinical phenotypes.
10.1212/WNL.0000000000211687
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.