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2022 (engelsk)Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 13, artikkel-id 2532Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]
Despite the success of genome-wide association studies, much of the genetic contribution to complex traits remains unexplained. Here, we analysed high coverage whole genome sequencing data, to evaluate the contribution of rare genetic variants to 414 plasma proteins. The frequency distribution of genetic variants was skewed towards the rare spectrum, and damaging variants were more often rare. We estimated that less than 4.3% of the narrow-sense heritability is expected to be explained by rare variants in our cohort. Using a gene-based approach, we identified Cis-associations for 237 of the proteins, which is slightly more compared to a GWAS (N=213), and we identified 34 loci in Trans. Several associations were driven by rare variants, and rare variants had on average larger phenotypic effects. We conclude therefore that rare variants could be of importance for precision medicine applications, but have a more limited contribution to the missing heritability of complex diseases.
sted, utgiver, år, opplag, sider
Springer Nature, 2022
Emneord
Rare variants, SKAT, Protein Biomarkers, Hidden heritability, Missing heritability, GWAS
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-470178 (URN)10.1038/s41467-022-30208-8 (DOI)000792848500027 ()35534486 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2019-01497Swedish Heart Lung Foundation, 20200687Knut and Alice Wallenberg FoundationScience for Life Laboratory, SciLifeLabSwedish National Infrastructure for Computing (SNIC), SNIC 2018/8-372Swedish Research Council, 2018-05973
Merknad
Titel in Thesis: The contribution of rare whole genome sequencing variants to plasma protein levels and to the missing heritability
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