TY - JOUR
T1 - Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes
AU - Assary, Elham
AU - Coleman, Jonathan
AU - Hemani, Gibran
AU - Van De Weijer, Margot
AU - Howe, Laurence J.
AU - Palviainen, Teemu
AU - Grasby, Katrina L.
AU - Ahlskog, Rafael
AU - Nygaard, Marianne
AU - Cheesman, Rosa
AU - Lim, Kai
AU - Reynolds, Chandra A.
AU - Ordoñana, Juan R
AU - Colodro-Conde, Lucia
AU - Gordon, Scott G
AU - Madrid-Valero, Juan J
AU - Thalamuthu, Anbupalam
AU - Hottenga, Jouke-Jan
AU - Mengel-From, Jonas
AU - Armstrong, Nicola J
AU - Sachdev, Perminder
AU - Lee, Teresa
AU - Brodaty, Henry
AU - Trollor, Julian N.
AU - Wright, Margaret J.
AU - Ames, David
AU - Catts, Vibeke S.
AU - Latvala, Antti
AU - Vuoksimaa, Eero
AU - Mallard, Travis T.
AU - Harden, K. Paige
AU - Tucker-drob, Elliot M.
AU - Oskarsson, Sven
AU - Hammond, Christopher J
AU - Christensen, Kaare
AU - Taylor, Mark J.
AU - Lundström, Sebastian
AU - Larsson, Henrik
AU - Karlsson, Robert
AU - Pedersen, Nancy L.
AU - Mather, Karen A.
AU - Medland, Sarah E.
AU - Boomsma, Dorret I.
AU - Martin, Nicholas G.
AU - Plomin, Robert
AU - Bartels, Meike
AU - Lichtenstein, Paul
AU - Kaprio, Jaakko
AU - Eley, Thalia
AU - Davies, Neil M.
AU - Munroe, Patricia B.
AU - Keers, Robert
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/6/10
Y1 - 2025/6/10
N2 - Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes, but these variants have proven challenging to detect. Genome-wide association studies of monozygotic twin differences are conducted through family-based variance analyses, which are more robust to the systemic biases that impact population-based methods. We combined data from 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct one of the largest genome-wide association study meta-analyses of monozygotic phenotypic differences, in children, adolescents and adults separately, for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism and wellbeing. The proportions of phenotypic variance explained by single-nucleotide polymorphisms in these phenotypes were estimated (h
2 = 0–18%), but were imprecise. We identified 13 genome-wide significant associations (single-nucleotide polymorphisms, genes and gene sets), including genes related to stress reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. This is the largest genetic study of monozygotic twins to date by an order of magnitude, evidencing an alternative method to study the genetic architecture of environmental sensitivity. The statistical power was limited for some analyses, calling for better-powered future studies.
AB - Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes, but these variants have proven challenging to detect. Genome-wide association studies of monozygotic twin differences are conducted through family-based variance analyses, which are more robust to the systemic biases that impact population-based methods. We combined data from 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct one of the largest genome-wide association study meta-analyses of monozygotic phenotypic differences, in children, adolescents and adults separately, for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism and wellbeing. The proportions of phenotypic variance explained by single-nucleotide polymorphisms in these phenotypes were estimated (h
2 = 0–18%), but were imprecise. We identified 13 genome-wide significant associations (single-nucleotide polymorphisms, genes and gene sets), including genes related to stress reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. This is the largest genetic study of monozygotic twins to date by an order of magnitude, evidencing an alternative method to study the genetic architecture of environmental sensitivity. The statistical power was limited for some analyses, calling for better-powered future studies.
UR - http://www.scopus.com/inward/record.url?scp=105007678976&partnerID=8YFLogxK
U2 - 10.1038/s41562-025-02193-7
DO - 10.1038/s41562-025-02193-7
M3 - Article
SN - 2397-3374
JO - Nature Human Behaviour
JF - Nature Human Behaviour
ER -