Loh Lab

New preprint on phenotypic impacts of rare copy number variants

We are excited to share a new preprint, “Influences of rare copy number variation on human complex traits” (Hujoel et al.), which explores the phenotypic impact of rare copy number variation in the human genome, discovering many new ways in which genetic variation shapes human traits. These analyses were enabled by a new computational approach we developed that substantially increases CNV detection power in large cohorts by pooling information across individuals who share extended SNP haplotypes. We applied this approach to SNP-array genotyping probe intensity data from UK Biobank (N~500K), detecting ~6-fold more CNVs that previous analyses, and accounting for approximately half of all rare gene inactivation events produced by genomic structural variation. Subsequent CNV-phenotype association and fine-mapping analyses identified CNVs at 97 loci (~75% novel) influencing human quantitative traits, many with large effect sizes (>1 standard deviation). CNVs at several loci created long allelic series that further elucidated the roles of gene dosage and regulatory elements in shaping human complex traits.