Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.
van der Laan Camiel M, Ip Hill F, Schipper Marijn, Hottenga Jouke-Jan, St Pourcain Beate, Zayats Tetyana, Pool René, Krapohl Eva M L, Brikell Isabell, Soler Artigas María, Cabana-Domínguez Judit, Llonga Natalia, Nolte Ilja M, Bolhuis Koen, Palviainen Teemu, Zafarmand Hadi, Gordon Scott, Aliev Fazil, Burt S Alexandra, Wang Carol A, Saunders Gretchen, Karhunen Ville, Adkins Daniel E, Border Richard, Peterson Roseann E, Prinz Joseph A, Thiering Elisabeth, Vilor-Tejedor Natàlia, Ahluwalia Tarunveer S, Allegrini Andrea, Rimfeld Kaili, Chen Qi, Lu Yi, Martin Joanna, Bosch Rosa, Ramos-Quiroga Josep Antoni, Neumann Alexander, Ensink Judith, Grasby Katrina L, Morosoli José J, Tong Xiaoran, Marrington Shelby, Scott James G, Shabalin Andrey A, Corley Robin, Evans Luke M, Sugden Karen, Alemany Silvia, Sass Lærke, Vinding Rebecca, Ehli Erik A, Hagenbeek Fiona A, Derks Eske M, Larsson Henrik, Snieder Harold, Cecil Charlotte, Whipp Alyce M, Korhonen Tellervo, Vuoksimaa Eero, Rose Richard J, Uitterlinden André G, Haavik Jan, Harris Jennifer R, Helgeland Øyvind, Johansson Stefan, Knudsen Gun Peggy S, Njolstad Pal Rasmus, Lu Qing, Rodriguez Alina, Henders Anjali K, Mamun Abdullah, Najman Jackob M, Brown Sandy, Hopfer Christian, Krauter Kenneth, Reynolds Chandra A, Smolen Andrew, Stallings Michael, Wadsworth Sally, Wall Tamara L, Eaves Lindon, Silberg Judy L, Miller Allison, Havdahl Alexandra, Llop Sabrina, Lopez-Espinosa Maria-Jose, Bønnelykke Klaus, Sunyer Jordi, Arseneault Louise, Standl Marie, Heinrich Joachim, Boden Joseph, Pearson John, Horwood John, Kennedy Martin, Poulton Richie, Maes Hermine H, Hewitt John, Copeland William E, Middeldorp Christel M, Williams Gail M, Wray Naomi, Järvelin Marjo-Riitta, McGue Matt, Iacono William, Caspi Avshalom, Moffitt Terrie E, Whitehouse Andrew J O, Pennell Craig E, Klump Kelly L, Jiang Chang, Dick Danielle M, Reichborn-Kjennerud Ted, Martin Nicholas G, Medland Sarah E, Vrijkotte Tanja, Kaprio Jaakko, Tiemeier Henning, Davey Smith George, Hartman Catharina A, Oldehinkel Albertine J, Casas Miquel, Ribasés Marta, Lichtenstein Paul, Lundström Sebastian, Plomin Robert, Bartels Meike, Nivard Michel G, Boomsma Dorret I
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Аннотация
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.
Для цитирования: van der Laan Camiel M, Ip Hill F, Schipper Marijn, Hottenga Jouke-Jan, St Pourcain Beate, Zayats Tetyana, Pool René, Krapohl Eva M L, Brikell Isabell, Soler Artigas María, Cabana-Domínguez Judit, Llonga Natalia, Nolte Ilja M, Bolhuis Koen, Palviainen Teemu, Zafarmand Hadi, Gordon Scott, Aliev Fazil, Burt S Alexandra, Wang Carol A, Saunders Gretchen, Karhunen Ville, Adkins Daniel E, Border Richard, Peterson Roseann E, Prinz Joseph A, Thiering Elisabeth, Vilor-Tejedor Natàlia, Ahluwalia Tarunveer S, Allegrini Andrea, Rimfeld Kaili, Chen Qi, Lu Yi, Martin Joanna, Bosch Rosa, Ramos-Quiroga Josep Antoni, Neumann Alexander, Ensink Judith, Grasby Katrina L, Morosoli José J, Tong Xiaoran, Marrington Shelby, Scott James G, Shabalin Andrey A, Corley Robin, Evans Luke M, Sugden Karen, Alemany Silvia, Sass Lærke, Vinding Rebecca, Ehli Erik A, Hagenbeek Fiona A, Derks Eske M, Larsson Henrik, Snieder Harold, Cecil Charlotte, Whipp Alyce M, Korhonen Tellervo, Vuoksimaa Eero, Rose Richard J, Uitterlinden André G, Haavik Jan, Harris Jennifer R, Helgeland Øyvind, Johansson Stefan, Knudsen Gun Peggy S, Njolstad Pal Rasmus, Lu Qing, Rodriguez Alina, Henders Anjali K, Mamun Abdullah, Najman Jackob M, Brown Sandy, Hopfer Christian, Krauter Kenneth, Reynolds Chandra A, Smolen Andrew, Stallings Michael, Wadsworth Sally, Wall Tamara L, Eaves Lindon, Silberg Judy L, Miller Allison, Havdahl Alexandra, Llop Sabrina, Lopez-Espinosa Maria-Jose, Bønnelykke Klaus, Sunyer Jordi, Arseneault Louise, Standl Marie, Heinrich Joachim, Boden Joseph, Pearson John, Horwood John, Kennedy Martin, Poulton Richie, Maes Hermine H, Hewitt John, Copeland William E, Middeldorp Christel M, Williams Gail M, Wray Naomi, Järvelin Marjo-Riitta, McGue Matt, Iacono William, Caspi Avshalom, Moffitt Terrie E, Whitehouse Andrew J O, Pennell Craig E, Klump Kelly L, Jiang Chang, Dick Danielle M, Reichborn-Kjennerud Ted, Martin Nicholas G, Medland Sarah E, Vrijkotte Tanja, Kaprio Jaakko, Tiemeier Henning, Davey Smith George, Hartman Catharina A, Oldehinkel Albertine J, Casas Miquel, Ribasés Marta, Lichtenstein Paul, Lundström Sebastian, Plomin Robert, Bartels Meike, Nivard Michel G, Boomsma Dorret I. Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.. Nature genetics. 2025. DOI: 10.1038/s41588-025-02295-y.
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