Protein-coding repeat polymorphisms strongly shape diverse human phenotypes

Abstract

Repeats associated with phenotype The degree to which repeated sequences within a genome affect human phenotypes has been difficult to establish. Mukamel et al . examined thousands of genomes in the UK Biobank and found that some of the largest effects of common genetic variants on human phenotypes, including those with clinical relevance, arise from protein-coding repeat polymorphisms (see the Perspective by Gymrek and Goren). Mapping the effects of the size and copy number of these repeated protein domains links genetic variation to human phenotypes, including lipoprotein(a) concentration, height, and male pattern balding. Furthermore, the alleles and frequencies of these repeated sequences differ between individuals of African and European descent, resulting in differences between the populations with clinical relevance for traits including lipoprotein(a) levels, a risk factor for coronary artery disease. —LMZ