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Title: Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p
Author: Weiner, Daniel J.
Ling, Emi
Erdin, Serkan
Tai, Derek J.C.
Yadav, Rachita
Grove, Jakob
Fu, Jack M.
Nadig, Ajay
Carey, Caitlin E.
Baya, Nikolas
Bybjerg Grauholm, Jonas
iPSYCH Consortium
Berretta, Sabina
Macosko, Evan Z.
Sebat, Jonathan
O'Connor, Luke J.
Hougaard, David M.
Børglum, Anders D.
Talkowski, Michael E.
McCarroll, Steven A.
Robinson, Elise B.
Keywords: Autisme
Genètica humana
Human genetics
Issue Date: 24-Oct-2022
Publisher: Nature Publishing Group
Abstract: The canonical paradigm for converting genetic association to mechanism involves iteratively mapping individual associations to the proximal genes through which they act. In contrast, in the present study we demonstrate the feasibility of extracting biological insights from a very large region of the genome and leverage this strategy to study the genetic influences on autism. Using a new statistical approach, we identified the 33-Mb p-arm of chromosome 16 (16p) as harboring the greatest excess of autism's common polygenic influences. The region also includes the mechanistically cryptic and autism-associated 16p11.2 copy number variant. Analysis of RNA-sequencing data revealed that both the common polygenic influences within 16p and the 16p11.2 deletion were associated with decreased average gene expression across 16p. The transcriptional effects of the rare deletion and diffuse common variation were correlated at the level of individual genes and analysis of Hi-C data revealed patterns of chromatin contact that may explain this transcriptional convergence. These results reflect a new approach for extracting biological insight from genetic association data and suggest convergence of common and rare genetic influences on autism at 16p.
Note: Reproducció del document publicat a:
It is part of: Nature Genetics, 2022, vol. 54, p. 1630-1639
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ISSN: 1061-4036
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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