Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes.
СтатьяTwin StudyМетаанализНазвание и аннотация: Перевод пока не подготовлен
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Assary Elham, Coleman Jonathan R I, Hemani Gibran, van de Weijer Margot P, Howe Laurence J, Palviainen Teemu, Grasby Katrina L, Ahlskog Rafael, Nygaard Marianne, Cheesman Rosa, Lim Kai, Reynolds Chandra A, Ordoñana Juan R, Colodro-Conde Lucia, Gordon Scott, Madrid-Valero Juan J, Thalamuthu Anbupalam, Hottenga Jouke-Jan, Mengel-From Jonas, Armstrong Nicola J, Sachdev Perminder S, Lee Teresa, Brodaty Henry, Trollor Julian N, Wright Margaret, Ames David, Catts Vibeke S, Latvala Antti, Within Family Consortium, Vuoksimaa Eero, Mallard Travis, Paige Harden K, Tucker-Drob Elliot M, Oskarsson Sven, Hammond Christopher J, Christensen Kaare, Taylor Mark, Lundström Sebastian, Larsson Henrik, Karlsson Robert, Pedersen Nancy L, Mather Karen A, Medland Sarah E, Boomsma Dorret I, Martin Nicholas G, Plomin Robert, Bartels Meike, Lichtenstein Paul, Kaprio Jaakko, Eley Thalia C, Davies Neil M, Munroe Patricia B, Keers Robert
Аннотация
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.