Genetic correlates of phenotypic heterogeneity in autism

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Genetic correlates of phenotypic heterogeneity in autism. / Warrier, Varun; Zhang, Xinhe; Reed, Patrick; Havdahl, Alexandra; Moore, Tyler M.; Cliquet, Freddy; Leblond, Claire S.; Rolland, Thomas; Rosengren, Anders; Caceres, Antonia San Jose; Hayward, Hannah; Crawley, Daisy; Faulkner, Jessica; Sabet, Jessica; Ellis, Claire; Oakley, Bethany; Loth, Eva; Charman, Tony; Murphy, Declan; Holt, Rosemary; Waldman, Jack; Upadhyay, Jessica; Gunby, Nicola; Lai, Meng Chuan; Renouf, Gwilym; Ruigrok, Amber; Taylor, Emily; Ziauddeen, Hisham; Deakin, Julia; di Bruttopilo, Sara Ambrosino; van Dijk, Sarai; Rijks, Yvonne; Koops, Tabitha; Douma, Miriam; Spaan, Alyssia; Selten, Iris; Steffers, Maarten; van Themaat, Anna Ver Loren; Bast, Nico; Baumeister, Sarah; O’Dwyer, Larry; Bours, Carsten; Rausch, Annika; von Rhein, Daniel; Cornelissen, Ineke; de Bruin, Yvette; Graauwmans, Maartje; Kostrzewa, Elzbieta; Werge, Thomas; Nordentoft, Merete; EU-AIMS LEAP; iPSYCH-Autism Working Group; Spectrum 10K and APEX Consortia.

I: Nature Genetics, Bind 54, Nr. 9, 2022, s. 1293-1304.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Warrier, V, Zhang, X, Reed, P, Havdahl, A, Moore, TM, Cliquet, F, Leblond, CS, Rolland, T, Rosengren, A, Caceres, ASJ, Hayward, H, Crawley, D, Faulkner, J, Sabet, J, Ellis, C, Oakley, B, Loth, E, Charman, T, Murphy, D, Holt, R, Waldman, J, Upadhyay, J, Gunby, N, Lai, MC, Renouf, G, Ruigrok, A, Taylor, E, Ziauddeen, H, Deakin, J, di Bruttopilo, SA, van Dijk, S, Rijks, Y, Koops, T, Douma, M, Spaan, A, Selten, I, Steffers, M, van Themaat, AVL, Bast, N, Baumeister, S, O’Dwyer, L, Bours, C, Rausch, A, von Rhein, D, Cornelissen, I, de Bruin, Y, Graauwmans, M, Kostrzewa, E, Werge, T, Nordentoft, M, EU-AIMS LEAP, iPSYCH-Autism Working Group & Spectrum 10K and APEX Consortia 2022, 'Genetic correlates of phenotypic heterogeneity in autism', Nature Genetics, bind 54, nr. 9, s. 1293-1304. https://doi.org/10.1038/s41588-022-01072-5

APA

Warrier, V., Zhang, X., Reed, P., Havdahl, A., Moore, T. M., Cliquet, F., Leblond, C. S., Rolland, T., Rosengren, A., Caceres, A. S. J., Hayward, H., Crawley, D., Faulkner, J., Sabet, J., Ellis, C., Oakley, B., Loth, E., Charman, T., Murphy, D., ... Spectrum 10K and APEX Consortia (2022). Genetic correlates of phenotypic heterogeneity in autism. Nature Genetics, 54(9), 1293-1304. https://doi.org/10.1038/s41588-022-01072-5

Vancouver

Warrier V, Zhang X, Reed P, Havdahl A, Moore TM, Cliquet F o.a. Genetic correlates of phenotypic heterogeneity in autism. Nature Genetics. 2022;54(9):1293-1304. https://doi.org/10.1038/s41588-022-01072-5

Author

Warrier, Varun ; Zhang, Xinhe ; Reed, Patrick ; Havdahl, Alexandra ; Moore, Tyler M. ; Cliquet, Freddy ; Leblond, Claire S. ; Rolland, Thomas ; Rosengren, Anders ; Caceres, Antonia San Jose ; Hayward, Hannah ; Crawley, Daisy ; Faulkner, Jessica ; Sabet, Jessica ; Ellis, Claire ; Oakley, Bethany ; Loth, Eva ; Charman, Tony ; Murphy, Declan ; Holt, Rosemary ; Waldman, Jack ; Upadhyay, Jessica ; Gunby, Nicola ; Lai, Meng Chuan ; Renouf, Gwilym ; Ruigrok, Amber ; Taylor, Emily ; Ziauddeen, Hisham ; Deakin, Julia ; di Bruttopilo, Sara Ambrosino ; van Dijk, Sarai ; Rijks, Yvonne ; Koops, Tabitha ; Douma, Miriam ; Spaan, Alyssia ; Selten, Iris ; Steffers, Maarten ; van Themaat, Anna Ver Loren ; Bast, Nico ; Baumeister, Sarah ; O’Dwyer, Larry ; Bours, Carsten ; Rausch, Annika ; von Rhein, Daniel ; Cornelissen, Ineke ; de Bruin, Yvette ; Graauwmans, Maartje ; Kostrzewa, Elzbieta ; Werge, Thomas ; Nordentoft, Merete ; EU-AIMS LEAP ; iPSYCH-Autism Working Group ; Spectrum 10K and APEX Consortia. / Genetic correlates of phenotypic heterogeneity in autism. I: Nature Genetics. 2022 ; Bind 54, Nr. 9. s. 1293-1304.

Bibtex

@article{3579db0bec8d444da9ed5bf32656cb8d,

title = "Genetic correlates of phenotypic heterogeneity in autism",

abstract = "The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.",

author = "Varun Warrier and Xinhe Zhang and Patrick Reed and Alexandra Havdahl and Moore, {Tyler M.} and Freddy Cliquet and Leblond, {Claire S.} and Thomas Rolland and Anders Rosengren and Caceres, {Antonia San Jose} and Hannah Hayward and Daisy Crawley and Jessica Faulkner and Jessica Sabet and Claire Ellis and Bethany Oakley and Eva Loth and Tony Charman and Declan Murphy and Rosemary Holt and Jack Waldman and Jessica Upadhyay and Nicola Gunby and Lai, {Meng Chuan} and Gwilym Renouf and Amber Ruigrok and Emily Taylor and Hisham Ziauddeen and Julia Deakin and {di Bruttopilo}, {Sara Ambrosino} and {van Dijk}, Sarai and Yvonne Rijks and Tabitha Koops and Miriam Douma and Alyssia Spaan and Iris Selten and Maarten Steffers and {van Themaat}, {Anna Ver Loren} and Nico Bast and Sarah Baumeister and Larry O{\textquoteright}Dwyer and Carsten Bours and Annika Rausch and {von Rhein}, Daniel and Ineke Cornelissen and {de Bruin}, Yvette and Maartje Graauwmans and Elzbieta Kostrzewa and Thomas Werge and Merete Nordentoft and {EU-AIMS LEAP} and {iPSYCH-Autism Working Group} and {Spectrum 10K and APEX Consortia}",

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

year = "2022",

doi = "10.1038/s41588-022-01072-5",

language = "English",

volume = "54",

pages = "1293--1304",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "nature publishing group",

number = "9",

}

RIS

TY - JOUR

T1 - Genetic correlates of phenotypic heterogeneity in autism

AU - Warrier, Varun

AU - Zhang, Xinhe

AU - Reed, Patrick

AU - Havdahl, Alexandra

AU - Moore, Tyler M.

AU - Cliquet, Freddy

AU - Leblond, Claire S.

AU - Rolland, Thomas

AU - Rosengren, Anders

AU - Caceres, Antonia San Jose

AU - Hayward, Hannah

AU - Crawley, Daisy

AU - Faulkner, Jessica

AU - Sabet, Jessica

AU - Ellis, Claire

AU - Oakley, Bethany

AU - Loth, Eva

AU - Charman, Tony

AU - Murphy, Declan

AU - Holt, Rosemary

AU - Waldman, Jack

AU - Upadhyay, Jessica

AU - Gunby, Nicola

AU - Lai, Meng Chuan

AU - Renouf, Gwilym

AU - Ruigrok, Amber

AU - Taylor, Emily

AU - Ziauddeen, Hisham

AU - Deakin, Julia

AU - di Bruttopilo, Sara Ambrosino

AU - van Dijk, Sarai

AU - Rijks, Yvonne

AU - Koops, Tabitha

AU - Douma, Miriam

AU - Spaan, Alyssia

AU - Selten, Iris

AU - Steffers, Maarten

AU - van Themaat, Anna Ver Loren

AU - Bast, Nico

AU - Baumeister, Sarah

AU - O’Dwyer, Larry

AU - Bours, Carsten

AU - Rausch, Annika

AU - von Rhein, Daniel

AU - Cornelissen, Ineke

AU - de Bruin, Yvette

AU - Graauwmans, Maartje

AU - Kostrzewa, Elzbieta

AU - Werge, Thomas

AU - Nordentoft, Merete

AU - EU-AIMS LEAP

AU - iPSYCH-Autism Working Group

AU - Spectrum 10K and APEX Consortia

PY - 2022

Y1 - 2022

N2 - The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.

AB - The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.

U2 - 10.1038/s41588-022-01072-5

DO - 10.1038/s41588-022-01072-5

M3 - Journal article

C2 - 35654973

AN - SCOPUS:85133877615

VL - 54

SP - 1293

EP - 1304

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -

ID: 325464660