Genetics of environmental sensitivity to psychiatric and neurodevelopmental phenotypes: evidence from GWAS of monozygotic twins.

Autor:	Assary E; Kings College London., Coleman J; Institute of Psychiatry, Psychology, and Neuroscience, King's College London., Hemani G; University of Bristol., van Der Veijer M; Vrije Universiteit Amsterdam., Howe L; University of Bristol., Palviainen T; Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki., Grasby K; QIMR Berghofer Medical Research Institute., Ahlskog R; Uppsala University., Nygaard M; Danish Twin Registry., Cheesman R; University of Oslo., Lim K; King's College London., Reynolds C; University of Colorado Boulder., Ordoñana J; University of Murcia., Colodro-Conde L; QIMR Berghofer Medical Research Institute., Gordon S; QIMR Berghofer Medical Research Institute., Madrid-Valero J; University of Murcia., Thalamuthu A; University of New South Wales., Hottenga JJ; Vrije Universiteit., Mengel-From J; University of Southern Denmark., Armstrong NJ; Curtin University., Sachdev P; University of New South Wales., Lee T; University of New South Wales., Brodaty H; Centre for Healthy Brain Ageing., Trollor J; University of New South Wales., Wright M; The University of Queensland., Ames D; University of Melbourne., Catts V; University of New South Wales., Latvala A; University of Helsinki., Vuoksimaa E; University of Helsinki., Mallard T; Massachusetts General Hospital., Harden K; University of Texas at Austin., Tucker-Drob E; The University of Texas at Austin., Oskarsson S; Uppsala University., Hammond C; King's College London., Christensen K; University of Southern Denmark., Taylor M; Karolinska Institutet., Lundström S; University of Gothenburg., Larsson H; Dummy., Karlsson R; Karolinska Institutet., Pedersen N; Karolinska Institute., Mather K; Centre for Healthy Brain Ageing, Psychiatry, University of New South Wales (UNSW)., Medland S; QIMR Berghofer Medical Research Institute., Boomsma D; Vrije Universiteit Amsterdam, The Netherlands., Martin N; QIMR Berghofer Medical Research Institute., Plomin R; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London., Bartels M; VU University Amsterdam., Lichtenstein P; Karolinska Institute., Kaprio J; University of Helsinki., Eley T; King's College London., Davies N; University College London., Munroe P; Queen Mary University of London., Keers R; Queen Mary University of London.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 May 02. Date of Electronic Publication: 2024 May 02.
DOI:	10.21203/rs.3.rs-4333635/v1
Abstrakt:	Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity. Competing Interests: Conflicts of interest The authors declare no conflicts of interest.
Databáze:	MEDLINE
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