TY - JOUR
T1 - Genetic correlates of phenotypic heterogeneity in autism
AU - EU-AIMS LEAP
AU - iPSYCH-Autism Working Group
AU - Spectrum 10K and APEX Consortia
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 - Cauvet, Elodie
AU - Tammimies, Kristiina
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/9
Y1 - 2022/9
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.
UR - http://www.scopus.com/inward/record.url?scp=85133877615&partnerID=8YFLogxK
U2 - 10.1038/s41588-022-01072-5
DO - 10.1038/s41588-022-01072-5
M3 - Article
C2 - 35654973
AN - SCOPUS:85133877615
SN - 1061-4036
VL - 54
SP - 1293
EP - 1304
JO - Nature Genetics
JF - Nature Genetics
IS - 9
ER -