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Rare Copy Number Variants (CNVs) in 100,000 European Ancestry Subjects unveil Multiple Disease Associations

By 11th February 2020No Comments

The following study was conducted by Scientists from The Children’s Hospital of Philadelphia, Pennsylvania; University of Pennsylvania, Philadelphia; University of California, San Francisco; University of Washington School of Medicine, Seattle, Washington; New Jersey Institute of Technology, Newark, USA; Institute of Guangzhou Medical University, Guangzhou, China; University La Sapienza, Rome, Italy. Study is published in Nature Communications Journal as detailed below.

Nature Communications (2020); Volume 11, Article number: 255

Rare Copy Number Variants in Over 100,000 European Ancestry Subjects Reveal Multiple Disease Associations


Copy number variants (CNVs) are suggested to have a widespread impact on the human genome and phenotypes. To understand the role of CNVs across human diseases, we examine the CNV genomic landscape of 100,028 unrelated individuals of European ancestry, using SNP and CGH array datasets. We observe an average CNV burden of ~650 kb, identifying a total of 11,314 deletion, 5625 duplication, and 2746 homozygous deletion CNV regions (CNVRs). In all, 13.7% are unreported, 58.6% overlap with at least one gene, and 32.8% interrupt coding exons. These CNVRs are significantly more likely to overlap OMIM genes (2.94-fold), GWAS loci (1.52-fold), and non-coding RNAs (1.44-fold), compared with random distribution (P < 1 × 10−3). We uncover CNV associations with four major disease categories, including autoimmune, cardio-metabolic, oncologic, and neurological/psychiatric diseases, and identify several drug-repurposing opportunities. Our results demonstrate robust frequency definition for large-scale rare variant association studies, identify CNVs associated with major disease categories, and illustrate the pleiotropic impact of CNVs in human disease.


Nature Communications



Li, Y.R., Glessner, J.T., Coe, B.P. et al. Rare copy number variants in over 100,000 European ancestry subjects reveal multiple disease associations. Nat Commun 11, 255 (2020).