Camiel M van der Laan,Hill F Ip,Marijn Schipper,Jouke-Jan Hottenga,Beate St Pourcain,Tetyana Zayats,René Pool,Eva M L Krapohl,Isabell Brikell,María Soler Artigas,Judit Cabana-Domínguez,Ilja M Nolte,Koen Bolhuis,Teemu Palviainen,Hadi Zafarmand,Scott Gordon,Fazil Aliev,S Alexandra Burt,Carol A Wang,Gretchen Saunders,Ville Karhunen,Daniel E Adkins,Richard Border,Roseann E Peterson,Joseph A Prinz,Elisabeth Thiering,Natàlia Vilor-Tejedor,Tarunveer S Ahluwalia,Andrea Allegrini,Kaili Rimfeld,Qi Chen,Yi Lu,Joanna Martin,Rosa Bosch,Josep Antoni Ramos-Quiroga,Alexander Neumann,Judith Ensink,Katrina L Grasby,José J Morosoli,Xiaoran Tong,Shelby Marrington,James G Scott,Andrey A Shabalin,Robin Corley,Luke M Evans,Karen Sugden,Silvia Alemany,Lærke Sass,Rebecca Vinding,Erik A Ehli,Fiona A Hagenbeek,Eske M Derks,Henrik Larsson,Harold Snieder,Charlotte Cecil,Alyce M Whipp,Tellervo Korhonen,Eero Vuoksimaa,Richard J Rose,André G Uitterlinden,Jan Haavik,Jennifer R Harris,Øyvind Helgeland,Stefan Johansson,Gun Peggy S Knudsen,Pal Rasmus Njolstad,Qing Lu,Alina Rodriguez,Anjali K Henders,Abdullah Mamun,Jackob M Najman,Sandy Brown,Christian Hopfer,Kenneth Krauter,Chandra A Reynolds,Andrew Smolen,Michael Stallings,Sally Wadsworth,Tamara L Wall,Lindon Eaves,Judy L Silberg,Allison Miller,Alexandra Havdahl,Sabrina Llop,Maria-Jose Lopez-Espinosa,Klaus Bønnelykke,Jordi Sunyer,Louise Arseneault,Marie Standl,Joachim Heinrich,Joseph Boden,John Pearson,John Horwood,Martin Kennedy,Richie Poulton,Hermine H Maes,John Hewitt,William E Copeland,Christel M Middeldorp,Gail M Williams,Naomi Wray,Marjo-Riitta Järvelin,Matt McGue,William Iacono,Avshalom Caspi,Terrie E Moffitt,Andrew J O Whitehouse,Craig E Pennell,Kelly L Klump,Chang Jiang,Danielle M Dick,Ted Reichborn-Kjennerud,Nicholas G Martin,Sarah E Medland,Tanja Vrijkotte,Jaakko Kaprio,Henning Tiemeier,George Davey Smith,Catharina A Hartman,Albertine J Oldehinkel,Miquel Casas,Marta Ribasés,Paul Lichtenstein,Sebastian Lundström,Robert Plomin,Meike Bartels,Michel G Nivard,Dorret I Boomsma,Natalia Llonga
{"title":"Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.","authors":"Camiel M van der Laan,Hill F Ip,Marijn Schipper,Jouke-Jan Hottenga,Beate St Pourcain,Tetyana Zayats,René Pool,Eva M L Krapohl,Isabell Brikell,María Soler Artigas,Judit Cabana-Domínguez,Ilja M Nolte,Koen Bolhuis,Teemu Palviainen,Hadi Zafarmand,Scott Gordon,Fazil Aliev,S Alexandra Burt,Carol A Wang,Gretchen Saunders,Ville Karhunen,Daniel E Adkins,Richard Border,Roseann E Peterson,Joseph A Prinz,Elisabeth Thiering,Natàlia Vilor-Tejedor,Tarunveer S Ahluwalia,Andrea Allegrini,Kaili Rimfeld,Qi Chen,Yi Lu,Joanna Martin,Rosa Bosch,Josep Antoni Ramos-Quiroga,Alexander Neumann,Judith Ensink,Katrina L Grasby,José J Morosoli,Xiaoran Tong,Shelby Marrington,James G Scott,Andrey A Shabalin,Robin Corley,Luke M Evans,Karen Sugden,Silvia Alemany,Lærke Sass,Rebecca Vinding,Erik A Ehli,Fiona A Hagenbeek,Eske M Derks,Henrik Larsson,Harold Snieder,Charlotte Cecil,Alyce M Whipp,Tellervo Korhonen,Eero Vuoksimaa,Richard J Rose,André G Uitterlinden,Jan Haavik,Jennifer R Harris,Øyvind Helgeland,Stefan Johansson,Gun Peggy S Knudsen,Pal Rasmus Njolstad,Qing Lu,Alina Rodriguez,Anjali K Henders,Abdullah Mamun,Jackob M Najman,Sandy Brown,Christian Hopfer,Kenneth Krauter,Chandra A Reynolds,Andrew Smolen,Michael Stallings,Sally Wadsworth,Tamara L Wall,Lindon Eaves,Judy L Silberg,Allison Miller,Alexandra Havdahl,Sabrina Llop,Maria-Jose Lopez-Espinosa,Klaus Bønnelykke,Jordi Sunyer,Louise Arseneault,Marie Standl,Joachim Heinrich,Joseph Boden,John Pearson,John Horwood,Martin Kennedy,Richie Poulton,Hermine H Maes,John Hewitt,William E Copeland,Christel M Middeldorp,Gail M Williams,Naomi Wray,Marjo-Riitta Järvelin,Matt McGue,William Iacono,Avshalom Caspi,Terrie E Moffitt,Andrew J O Whitehouse,Craig E Pennell,Kelly L Klump,Chang Jiang,Danielle M Dick,Ted Reichborn-Kjennerud,Nicholas G Martin,Sarah E Medland,Tanja Vrijkotte,Jaakko Kaprio,Henning Tiemeier,George Davey Smith,Catharina A Hartman,Albertine J Oldehinkel,Miquel Casas,Marta Ribasés,Paul Lichtenstein,Sebastian Lundström,Robert Plomin,Meike Bartels,Michel G Nivard,Dorret I Boomsma,Natalia Llonga","doi":"10.1038/s41588-025-02295-y","DOIUrl":null,"url":null,"abstract":"We performed a genome-wide association meta-analysis (GWAMA) of 290,134 attention-deficit/hyperactivity disorder (ADHD) symptom measures of 70,953 unique individuals from multiple raters, ages and instruments (ADHDSYMP). Next, we meta-analyzed the results with a study of ADHD diagnosis (ADHDOVERALL). ADHDSYMP returned no genome-wide significant variants. We show that the combined ADHDOVERALL GWAMA identified 39 independent loci, of which 17 were new. Using a recently developed gene-mapping method, Fine-mapped Locus Assessment Model of Effector genes, we identified 22 potential ADHD effector genes implicating several new biological processes and pathways. Moderate negative genetic correlations (rg < -0.40) were observed with multiple cognitive traits. In three cohorts, polygenic scores (PGSs) based on ADHDOVERALL outperformed PGSs based on ADHD symptoms and diagnosis alone. Our findings support the notion that clinical ADHD is at the extreme end of a continuous liability that is indexed by ADHD symptoms. We show that including ADHD symptom counts helps to identify new genes implicated in ADHD.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"1 1","pages":""},"PeriodicalIF":29.0000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41588-025-02295-y","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
We performed a genome-wide association meta-analysis (GWAMA) of 290,134 attention-deficit/hyperactivity disorder (ADHD) symptom measures of 70,953 unique individuals from multiple raters, ages and instruments (ADHDSYMP). Next, we meta-analyzed the results with a study of ADHD diagnosis (ADHDOVERALL). ADHDSYMP returned no genome-wide significant variants. We show that the combined ADHDOVERALL GWAMA identified 39 independent loci, of which 17 were new. Using a recently developed gene-mapping method, Fine-mapped Locus Assessment Model of Effector genes, we identified 22 potential ADHD effector genes implicating several new biological processes and pathways. Moderate negative genetic correlations (rg < -0.40) were observed with multiple cognitive traits. In three cohorts, polygenic scores (PGSs) based on ADHDOVERALL outperformed PGSs based on ADHD symptoms and diagnosis alone. Our findings support the notion that clinical ADHD is at the extreme end of a continuous liability that is indexed by ADHD symptoms. We show that including ADHD symptom counts helps to identify new genes implicated in ADHD.
期刊介绍：
Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation.
Integrative genetic topics comprise, but are not limited to:
-Genes in the pathology of human disease
-Molecular analysis of simple and complex genetic traits
-Cancer genetics
-Agricultural genomics
-Developmental genetics
-Regulatory variation in gene expression
-Strategies and technologies for extracting function from genomic data
-Pharmacological genomics
-Genome evolution
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