FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3195755841> ?p ?o ?g. }

• W3195755841 abstract "Abstract Recent works have shown that SNP-heritability—which is dominated by low-effect common variants—may not be the most relevant quantity for localizing high-effect/critical disease genes. Here, we introduce methods to estimate the proportion of phenotypic variance explained by a given assignment of SNPs to a single gene ( genelevel heritability ). We partition gene-level heritability across minor allele frequency (MAF) classes to find genes whose gene-level heritability is explained exclusively by “low-frequency/rare” variants (0.5% ≤ MAF < 1%). Applying our method to ~17K protein-coding genes and 25 quantitative traits in the UK Biobank (N=290K), we find that, on average across traits, ~2.5% of nonzero-heritability genes have a rare-variant component, and only ~0.8% (370 gene-trait pairs) have heritability exclusively from rare variants. Of these 370 gene-trait pairs, 37% were not detected by existing gene-level association testing methods, likely because existing methods combine signal from all variants in a region irrespective of MAF class. Many of the additional genes we identify are implicated in phenotypically related Mendelian disorders or congenital developmental disorders, providing further evidence of their trait-relevance. Notably, the rare-variant component of gene-level heritability exhibits trends different from those of common-variant gene-level heritability. For example, while total gene-level heritability increases with gene length, the rare-variant component is significantly larger among shorter genes; the cumulative distributions of gene-level heritability also vary across traits and reveal differences in the relative contributions of rare/common variants to overall gene-level polygenicity. We conclude that the proportion of gene-level heritability attributable to low-frequency/rare variation can yield novel insights into complex-trait genetic architecture." @default.
• W3195755841 created "2021-08-30" @default.
• W3195755841 creator A5002446630 @default.
• W3195755841 creator A5013091003 @default.
• W3195755841 creator A5029941351 @default.
• W3195755841 creator A5040739184 @default.
• W3195755841 creator A5041292890 @default.
• W3195755841 creator A5057630970 @default.
• W3195755841 creator A5062800512 @default.
• W3195755841 date "2021-08-18" @default.
• W3195755841 modified "2023-10-17" @default.
• W3195755841 title "Partitioning gene-level contributions to complex-trait heritability by allele frequency identifies disease-relevant genes" @default.
• W3195755841 cites W1550732922 @default.
• W3195755841 cites W1768346277 @default.
• W3195755841 cites W1844405070 @default.
• W3195755841 cites W1973772928 @default.
• W3195755841 cites W1984960406 @default.
• W3195755841 cites W1986818660 @default.
• W3195755841 cites W1988470091 @default.
• W3195755841 cites W1989317600 @default.
• W3195755841 cites W1990430353 @default.
• W3195755841 cites W1991897687 @default.
• W3195755841 cites W1995781250 @default.
• W3195755841 cites W1998221042 @default.
• W3195755841 cites W1999999098 @default.
• W3195755841 cites W2020427316 @default.
• W3195755841 cites W2020506534 @default.
• W3195755841 cites W2038522196 @default.
• W3195755841 cites W2051314902 @default.
• W3195755841 cites W2061623413 @default.
• W3195755841 cites W2063655230 @default.
• W3195755841 cites W2065473485 @default.
• W3195755841 cites W2070984858 @default.
• W3195755841 cites W2078059415 @default.
• W3195755841 cites W2087936498 @default.
• W3195755841 cites W2093636770 @default.
• W3195755841 cites W2098188199 @default.
• W3195755841 cites W2098644602 @default.
• W3195755841 cites W2100909778 @default.
• W3195755841 cites W2101686982 @default.
• W3195755841 cites W2103858001 @default.
• W3195755841 cites W2104549677 @default.
• W3195755841 cites W2129559300 @default.
• W3195755841 cites W2134460361 @default.
• W3195755841 cites W2134585221 @default.
• W3195755841 cites W2136112893 @default.
• W3195755841 cites W2139584915 @default.
• W3195755841 cites W2140149531 @default.
• W3195755841 cites W2143146488 @default.
• W3195755841 cites W2146415150 @default.
• W3195755841 cites W2154920687 @default.
• W3195755841 cites W2155496693 @default.
• W3195755841 cites W2157929834 @default.
• W3195755841 cites W2158802660 @default.
• W3195755841 cites W2159417227 @default.
• W3195755841 cites W2162151166 @default.
• W3195755841 cites W2163953557 @default.
• W3195755841 cites W2168354474 @default.
• W3195755841 cites W2188707104 @default.
• W3195755841 cites W2198653738 @default.
• W3195755841 cites W2229599978 @default.
• W3195755841 cites W2256016639 @default.
• W3195755841 cites W2264585211 @default.
• W3195755841 cites W2280070832 @default.
• W3195755841 cites W2280781077 @default.
• W3195755841 cites W2290463362 @default.
• W3195755841 cites W2316018497 @default.
• W3195755841 cites W2325392078 @default.
• W3195755841 cites W2338936928 @default.
• W3195755841 cites W2469213152 @default.
• W3195755841 cites W2584469054 @default.
• W3195755841 cites W2609272369 @default.
• W3195755841 cites W2626606138 @default.
• W3195755841 cites W2725988230 @default.
• W3195755841 cites W2766295673 @default.
• W3195755841 cites W2766863318 @default.
• W3195755841 cites W2791118826 @default.
• W3195755841 cites W2800582290 @default.
• W3195755841 cites W2804434811 @default.
• W3195755841 cites W2808363286 @default.
• W3195755841 cites W2891792152 @default.
• W3195755841 cites W2892391774 @default.
• W3195755841 cites W2895486342 @default.
• W3195755841 cites W2901957554 @default.
• W3195755841 cites W2923424663 @default.
• W3195755841 cites W2934861239 @default.
• W3195755841 cites W2952835495 @default.
• W3195755841 cites W2953945894 @default.
• W3195755841 cites W2954752112 @default.
• W3195755841 cites W2966010373 @default.
• W3195755841 cites W2966861845 @default.
• W3195755841 cites W2970142068 @default.
• W3195755841 cites W2972391824 @default.
• W3195755841 cites W3015904164 @default.
• W3195755841 cites W3025047014 @default.
• W3195755841 cites W3025060722 @default.
• W3195755841 cites W3038072559 @default.
• W3195755841 cites W3042068575 @default.
• W3195755841 cites W3048701096 @default.
• W3195755841 cites W3102939328 @default.

• next