Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability

• DOI: 10.1038/s41467-022-30208-8
• Publication Date: 2022-05-09T10:03:05Z
• Authors: Marcin Kierczak; Nima Rafati; Julia Höglund; Hadrien Gourlé; Valeria Lo Faro; Daniel Schmitz; Weronica E. Ek; Ulf Gyllensten; Stefan Enroth; Diana Ekman; Björn Nystedt; Torgny Karlsson; Åsa Johansson
• Keywords: Missing heritability problem; Genome-wide Association Study; Genetic Association

Abstract Despite the success of genome-wide association studies, much genetic contribution to complex traits remains unexplained. Here, we analyse high coverage whole-genome sequencing data, evaluate rare variants 414 plasma proteins. The frequency distribution is skewed towards spectrum, and damaging are more often rare. We estimate that less than 4.3% narrow-sense heritability expected be explained by in our cohort. Using a gene-based approach, identify Cis -associations for 237 proteins, which slightly compared GWAS ( N = 213), 34 associated loci Trans . Several associations driven variants, have larger effects, on average. therefore conclude could importance precision medicine applications, but limited missing diseases.