Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes.
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Assary E, Coleman JRI, Hemani G, van de Weijer MP, Howe LJ, Palviainen T, Grasby KL, Ahlskog R, Nygaard M, Cheesman R, Lim K, Reynolds CA, Ordoñana JR, Colodro-Conde L, Gordon S, Madrid-Valero JJ, Thalamuthu A, Hottenga JJ, Mengel-From J, Armstrong NJ, Sachdev PS, Lee T, Brodaty H, Trollor JN, Wright M, Ames D, Catts VS, Latvala A, Within Family Consortium , Vuoksimaa E, Mallard T, Paige Harden K, Tucker-Drob EM, Oskarsson S, Hammond CJ, Christensen K, Taylor M, Lundström S, Larsson H, Karlsson R, Pedersen NL, Mather KA, Medland SE, Boomsma DI, Martin NG, Plomin R, Bartels M, Lichtenstein P, Kaprio J, Eley TC, Davies NM, Munroe PB, Keers R
Nat Hum Behav 9 (8) 1683-1696 [2025-08-00; online 2025-06-10]
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 (h2 = 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.
NGI Uppsala (SNP&SEQ Technology Platform) [Service]
National Genomics Infrastructure [Service]
PubMed 40494901
DOI 10.1038/s41562-025-02193-7
Crossref 10.1038/s41562-025-02193-7
pmc: PMC12367547
pii: 10.1038/s41562-025-02193-7