Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
40494901
TITLE
Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes.
ABSTRACT
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  = 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.
© 2025. The Author(s).
DATE PUBLISHED
2025 Jun 10
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2024/04/27
accepted 2025/03/28
pubmed 2025/06/11 00:27
medline 2025/06/11 00:27
entrez 2025/06/10 23:16
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Assary E Assary Elham E Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. elham.1.assary@kcl.ac.uk.
Coleman JRI Coleman Jonathan R I JRI NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.
Hemani G Hemani Gibran G Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
van de Weijer MP van de Weijer Margot P MP Amsterdam Public Health Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Howe LJ Howe Laurence J LJ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Palviainen T Palviainen Teemu T Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Grasby KL Grasby Katrina L KL School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
Ahlskog R Ahlskog Rafael R Department of Government, Uppsala University, Uppsala, Sweden.
Nygaard M Nygaard Marianne M Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Cheesman R Cheesman Rosa R The PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
Lim K Lim Kai K Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Reynolds CA Reynolds Chandra A CA Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Ordoñana JR Ordoñana Juan R JR Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain.
Colodro-Conde L Colodro-Conde Lucia L School of Psychology, University of Queensland, Brisbane, Queensland, Australia.
Gordon S Gordon Scott S QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Madrid-Valero JJ Madrid-Valero Juan J JJ Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain.
Thalamuthu A Thalamuthu Anbupalam A Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Hottenga JJ Hottenga Jouke-Jan JJ Amsterdam Public Health Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Mengel-From J Mengel-From Jonas J Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Armstrong NJ Armstrong Nicola J NJ School of Electrical Engineering, Computing and Mathematical Sciences, Curtin University, Perth, Western Australia, Australia.
Sachdev PS Sachdev Perminder S PS Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Lee T Lee Teresa T Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Brodaty H Brodaty Henry H Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Trollor JN Trollor Julian N JN National Centre of Excellence in Intellectual Disability Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Wright M Wright Margaret M Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Ames D Ames David D University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Melbourne, Victoria, Australia.
Catts VS Catts Vibeke S VS Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Latvala A Latvala Antti A Institute of Criminology and Legal Policy, University of Helsinki, Helsinki, Finland.
Within Family Consortium
Vuoksimaa E Vuoksimaa Eero E Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Mallard T Mallard Travis T Center for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Paige Harden K Paige Harden K K Department of Psychology and Population Research Center, University of Texas at Austin, Austin, TX, USA.
Tucker-Drob EM Tucker-Drob Elliot M EM Department of Psychology and Population Research Center, University of Texas at Austin, Austin, TX, USA.
Oskarsson S Oskarsson Sven S Department of Government, Uppsala University, Uppsala, Sweden.
Hammond CJ Hammond Christopher J CJ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Christensen K Christensen Kaare K Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark.
Taylor M Taylor Mark M Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Lundström S Lundström Sebastian S Office for Psychiatry, Habilitation and Aid, Child and Adolescent Mental Health Services, Malmö, Sweden.
Larsson H Larsson Henrik H Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Karlsson R Karlsson Robert R Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Pedersen NL Pedersen Nancy L NL Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Mather KA Mather Karen A KA Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Boomsma DI Boomsma Dorret I DI Amsterdam Reproduction and Development research institute, Amsterdam, the Netherlands.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Plomin R Plomin Robert R Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Bartels M Bartels Meike M Amsterdam Public Health Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Lichtenstein P Lichtenstein Paul P Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Eley TC Eley Thalia C TC NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.
Davies NM Davies Neil M NM Department of Statistical Science, University College London, London, UK.
Munroe PB Munroe Patricia B PB William Harvey Research Institute, Queen Mary University of London, London, UK.
Keers R Keers Robert R School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Walters Robin G RG
Morris Sam S
Chen Zhengming Z
Lin Kuang K
Hughes Amanda M AM
Millwood Iona Y IY
Li Liming L
Havdahl Alexandra A
Pingault Jean-Baptiste JB
Hill W David WD
Boivin Michel M
Benjamin Daniel J DJ
Keller Matthew C MC
Torvik Fartein A FA
Li Shuai S
de Geus Eco E
Huider Floris F
Akingbuwa Wonu W
Ask Helga H
Magnus Per P
Åsvold Bjørn Olav BO
Brescianini Sonia S
Giannelis Alexandros A
Willoughby Emily A EA
Sung Joohon J
Lee Soo Ji SJ
Pyun Hyojin H
Evans David D
Archie Campbell C
JOURNAL
VOLUME:
ISSUE:
TITLE: Nature human behaviour
ISOABBREVIATION: Nat Hum Behav
YEAR: 2025
MONTH: Jun
DAY: 10
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2397-3374
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Hum Behav
COUNTRY: England
ISSNLINKING: 2397-3374
NLMUNIQUEID: 101697750
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
208881/Z/17/Z Wellcome Trust (Wellcome)
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