Educational attainment (EA), socioeconomic status (SES) and cognition are phenotypically and genetically linked to health outcomes. However, the role of copy number variations (CNVs) in influencing EA/SES/cognition remains unclear. 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. 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.

教育程度 (EA)、社会经济地位 (SES) 和认知在表型和遗传上与健康结果相关。然而，拷贝数变异 (CNV) 在影响 EA/SES/认知方面的作用仍不清楚。通过大规模 ( n = 305,401) 全基因组 CNV 水平关联分析，我们发现了 33 个与 EA/SES/认知显着相关的 CNV 位点，其中 20 个是新的（2p22.2、2p16.2、2p12 处的缺失） 、3p25.3、4p15.2、5p15.33、5q21.1、8p21.3、9p21.1、11p14.3、13q12.13、17q21.31 和 20q13.33，以及 3q12.2 处的重复、3q23、7p22.3、8p23.1、8p23.2、17q12 (105 kb) 和 19q13.32)。基因水平测试中鉴定出的基因在神经退行性变、端粒维持和轴突引导等生物学途径中丰富。全表型关联研究进一步确定了 EA/SES/认知相关 CNV 与精神和身体疾病的新关联，例如 6q27 重复与上呼吸道疾病和 17q12 (105 kb) 重复与情绪障碍。我们的研究结果为 EA/SES/认知提供了全基因组 CNV 谱，并弥合了它们与健康的联系。扩展的候选CNV数据库和驻留基因将成为未来研究的宝贵资源，旨在揭示认知功能和相关临床表型背后的生物学机制。