Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p

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Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p. / Weiner, Daniel J.; Ling, Emi; Erdin, Serkan; Tai, Derek J.C.; Yadav, Rachita; Grove, Jakob; Fu, Jack M.; Nadig, Ajay; Carey, Caitlin; Baya, Nikolas; Bybjerg-Grauholm, Jonas; Mortensen, Preben B.; Werge, Thomas; Demontis, Ditte; Mors, Ole; Nordentoft, Merete; Als, Thomas D.; Baekvad-Hansen, Marie; Rosengren, Anders; Havdahl, Alexandra; Hedemand, Anne; Palotie, Aarno; Chakravarti, Aravinda; Arking, Dan; Sulovari, Arvis; Starnawska, Anna; Thiruvahindrapuram, Bhooma; de Leeuw, Christiaan; Carey, Caitlin; Ladd-Acosta, Christine; van der Merwe, Celia; Devlin, Bernie; Cook, Edwin H.; Eichler, Evan; Corfield, Elisabeth; Dieleman, Gwen; Schellenberg, Gerard; Hakonarson, Hakon; Coon, Hilary; Dziobek, Isabel; Vorstman, Jacob; Girault, Jessica; Sutcliffe, James S.; Duan, Jinjie; Nurnberger, John; Hallmayer, Joachim; Buxbaum, Joseph; Hinney, Anke; Larsson, Henrik; Dalsgaard, Soren; iPSYCH Consortium; ASD Working Group of the Psychiatric Genomics Consortium; ADHD Working Group of the Psychiatric Genomics Consortium.

I: Nature Genetics, Bind 54, 2022, s. 1630-1639.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Weiner, DJ, Ling, E, Erdin, S, Tai, DJC, Yadav, R, Grove, J, Fu, JM, Nadig, A, Carey, C, Baya, N, Bybjerg-Grauholm, J, Mortensen, PB, Werge, T, Demontis, D, Mors, O, Nordentoft, M, Als, TD, Baekvad-Hansen, M, Rosengren, A, Havdahl, A, Hedemand, A, Palotie, A, Chakravarti, A, Arking, D, Sulovari, A, Starnawska, A, Thiruvahindrapuram, B, de Leeuw, C, Carey, C, Ladd-Acosta, C, van der Merwe, C, Devlin, B, Cook, EH, Eichler, E, Corfield, E, Dieleman, G, Schellenberg, G, Hakonarson, H, Coon, H, Dziobek, I, Vorstman, J, Girault, J, Sutcliffe, JS, Duan, J, Nurnberger, J, Hallmayer, J, Buxbaum, J, Hinney, A, Larsson, H, Dalsgaard, S, iPSYCH Consortium, ASD Working Group of the Psychiatric Genomics Consortium & ADHD Working Group of the Psychiatric Genomics Consortium 2022, 'Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p', Nature Genetics, bind 54, s. 1630-1639. https://doi.org/10.1038/s41588-022-01203-y

APA

Weiner, D. J., Ling, E., Erdin, S., Tai, D. J. C., Yadav, R., Grove, J., Fu, J. M., Nadig, A., Carey, C., Baya, N., Bybjerg-Grauholm, J., Mortensen, P. B., Werge, T., Demontis, D., Mors, O., Nordentoft, M., Als, T. D., Baekvad-Hansen, M., Rosengren, A., ... ADHD Working Group of the Psychiatric Genomics Consortium (2022). Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p. Nature Genetics, 54, 1630-1639. https://doi.org/10.1038/s41588-022-01203-y

Vancouver

Weiner DJ, Ling E, Erdin S, Tai DJC, Yadav R, Grove J o.a. Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p. Nature Genetics. 2022;54:1630-1639. https://doi.org/10.1038/s41588-022-01203-y

Author

Weiner, Daniel J. ; Ling, Emi ; Erdin, Serkan ; Tai, Derek J.C. ; Yadav, Rachita ; Grove, Jakob ; Fu, Jack M. ; Nadig, Ajay ; Carey, Caitlin ; Baya, Nikolas ; Bybjerg-Grauholm, Jonas ; Mortensen, Preben B. ; Werge, Thomas ; Demontis, Ditte ; Mors, Ole ; Nordentoft, Merete ; Als, Thomas D. ; Baekvad-Hansen, Marie ; Rosengren, Anders ; Havdahl, Alexandra ; Hedemand, Anne ; Palotie, Aarno ; Chakravarti, Aravinda ; Arking, Dan ; Sulovari, Arvis ; Starnawska, Anna ; Thiruvahindrapuram, Bhooma ; de Leeuw, Christiaan ; Carey, Caitlin ; Ladd-Acosta, Christine ; van der Merwe, Celia ; Devlin, Bernie ; Cook, Edwin H. ; Eichler, Evan ; Corfield, Elisabeth ; Dieleman, Gwen ; Schellenberg, Gerard ; Hakonarson, Hakon ; Coon, Hilary ; Dziobek, Isabel ; Vorstman, Jacob ; Girault, Jessica ; Sutcliffe, James S. ; Duan, Jinjie ; Nurnberger, John ; Hallmayer, Joachim ; Buxbaum, Joseph ; Hinney, Anke ; Larsson, Henrik ; Dalsgaard, Soren ; iPSYCH Consortium ; ASD Working Group of the Psychiatric Genomics Consortium ; ADHD Working Group of the Psychiatric Genomics Consortium. / Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p. I: Nature Genetics. 2022 ; Bind 54. s. 1630-1639.

Bibtex

@article{ac8ea3bd349e460d89d52723ee7ac0ba,

title = "Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p",

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{\textquoteright}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.",

author = "Weiner, {Daniel J.} and Emi Ling and Serkan Erdin and Tai, {Derek J.C.} and Rachita Yadav and Jakob Grove and Fu, {Jack M.} and Ajay Nadig and Caitlin Carey and Nikolas Baya and Jonas Bybjerg-Grauholm and Mortensen, {Preben B.} and Thomas Werge and Ditte Demontis and Ole Mors and Merete Nordentoft and Als, {Thomas D.} and Marie Baekvad-Hansen and Anders Rosengren and Alexandra Havdahl and Anne Hedemand and Aarno Palotie and Aravinda Chakravarti and Dan Arking and Arvis Sulovari and Anna Starnawska and Bhooma Thiruvahindrapuram and {de Leeuw}, Christiaan and Caitlin Carey and Christine Ladd-Acosta and {van der Merwe}, Celia and Bernie Devlin and Cook, {Edwin H.} and Evan Eichler and Elisabeth Corfield and Gwen Dieleman and Gerard Schellenberg and Hakon Hakonarson and Hilary Coon and Isabel Dziobek and Jacob Vorstman and Jessica Girault and Sutcliffe, {James S.} and Jinjie Duan and John Nurnberger and Joachim Hallmayer and Joseph Buxbaum and Anke Hinney and Henrik Larsson and Soren Dalsgaard and {iPSYCH Consortium} and {ASD Working Group of the Psychiatric Genomics Consortium} and {ADHD Working Group of the Psychiatric Genomics Consortium}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

doi = "10.1038/s41588-022-01203-y",

language = "English",

volume = "54",

pages = "1630--1639",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p

AU - Weiner, Daniel J.

AU - Ling, Emi

AU - Erdin, Serkan

AU - Tai, Derek J.C.

AU - Yadav, Rachita

AU - Grove, Jakob

AU - Fu, Jack M.

AU - Nadig, Ajay

AU - Carey, Caitlin

AU - Baya, Nikolas

AU - Bybjerg-Grauholm, Jonas

AU - Mortensen, Preben B.

AU - Werge, Thomas

AU - Demontis, Ditte

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Als, Thomas D.

AU - Baekvad-Hansen, Marie

AU - Rosengren, Anders

AU - Havdahl, Alexandra

AU - Hedemand, Anne

AU - Palotie, Aarno

AU - Chakravarti, Aravinda

AU - Arking, Dan

AU - Sulovari, Arvis

AU - Starnawska, Anna

AU - Thiruvahindrapuram, Bhooma

AU - de Leeuw, Christiaan

AU - Carey, Caitlin

AU - Ladd-Acosta, Christine

AU - van der Merwe, Celia

AU - Devlin, Bernie

AU - Cook, Edwin H.

AU - Eichler, Evan

AU - Corfield, Elisabeth

AU - Dieleman, Gwen

AU - Schellenberg, Gerard

AU - Hakonarson, Hakon

AU - Coon, Hilary

AU - Dziobek, Isabel

AU - Vorstman, Jacob

AU - Girault, Jessica

AU - Sutcliffe, James S.

AU - Duan, Jinjie

AU - Nurnberger, John

AU - Hallmayer, Joachim

AU - Buxbaum, Joseph

AU - Hinney, Anke

AU - Larsson, Henrik

AU - Dalsgaard, Soren

AU - iPSYCH Consortium

AU - ASD Working Group of the Psychiatric Genomics Consortium

AU - ADHD Working Group of the Psychiatric Genomics Consortium

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1038/s41588-022-01203-y

DO - 10.1038/s41588-022-01203-y

M3 - Journal article

C2 - 36280734

AN - SCOPUS:85140719036

VL - 54

SP - 1630

EP - 1639

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -

ID: 324384192