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Review
. 2023 Oct:153:105313.
doi: 10.1016/j.neubiorev.2023.105313. Epub 2023 Jul 13.

Genetic architecture of ADHD and overlap with other psychiatric disorders and cognition-related phenotypes

M Ribasés  1 , M Mitjans  2 , C A Hartman  3 , M Soler Artigas  1 , D Demontis  4 , H Larsson  5 , J A Ramos-Quiroga  6 , J Kuntsi  7 , S V Faraone  8 , A D Børglum  9 , A Reif  10 , B Franke  11 , B Cormand  12
Affiliations
Review

Genetic architecture of ADHD and overlap with other psychiatric disorders and cognition-related phenotypes

M Ribasés et al. Neurosci Biobehav Rev. 2023 Oct.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) co-occurs with many other psychiatric disorders and traits. In this review, we summarize and interpret the existing literature on the genetic architecture of these comorbidities based on hypothesis-generating approaches. Quantitative genetic studies indicate that genetic factors play a substantial role in the observed co-occurrence of ADHD with many different disorders and traits. Molecular genetic correlations derived from genome-wide association studies and results of studies based on polygenic risk scores confirm the general pattern but provide effect estimates that are smaller than those from twin studies. The identification of the specific genetic variants and biological pathways underlying co-occurrence using genome-wide approaches is still in its infancy. The first analyses of causal inference using genetic data support causal relationships between ADHD and comorbid disorders, although bidirectional effects identified in some instances point to complex relationships. While several issues in the methodology and inferences from the results are still to be overcome, this review shows that the co-occurrence of ADHD with many psychiatric disorders and traits is genetically interpretable.

Keywords: Attention-deficit/hyperactivity disorder; Comorbitidy; Cross-disorder genetics; Genetic correlation; Genome-wide association study; Pleiotropy; Polygenic risk score.

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Conflict of interest statement

Declaration of Competing Interest In the past year, S Faraone received income, potential income, travel expenses continuing education support and/or research support from Rhodes, OnDosis, Tris, Otsuka, Arbor, Ironshore, KemPharm/Corium, Akili, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is Program Director of www.adhdinadults.com. H Larsson reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals and Evolan Pharma AB; and sponsorship for a conference on attention-deficit/hyperactivity disorder from Shire/Takeda Pharmaceuticals and Evolan Pharma AB, all outside the submitted work. J Kuntsi has given talks at educational events sponsored by Medice; all funds are received by King’s College London and used for studies of ADHD. B Franke has received educational speaking fees from Medice; all funds were received by Radboud University Medical Center and used for research. JA Ramos-Quiroga was on the speakers’ bureau and/or acted as consultant for Biogen, Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the last 3 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 3 years: Janssen-Cilag, Shire, Oryzon, Roche, Psious, and Rubió. D Demontis has received speaker fee from Medici Nordic. AD Børglum has received speaker fee from Lundbeck. The rest of the authors do not declare any conflict of interest.

Figures

Fig. 1.
Fig. 1.
Schematic representation of genetic correlations reported between ADHD and other psychiatric disorders (left panel) and behavioural and cognitive traits (right panel). Positive correlations are presented in solid lines and negative correlations in dashed lines. The line width corresponds to the strength of the correlation. (a) Grotzinger et al. (2022); (b) Johnson et al. (2020); (c) Cabana-Domínguez et al. (2019); (d) Walters et al. (2018); (e) Kranzler et al. (2019); (f) Demontis et al. (2021); (g) Liu et al. (2019); (h) Zhou et al. (2020); (i)Sanchez-Roige et al. (2019a) (j) Pasman et al. (2018); (k)Demontis et al. (2019b). *Drug-related phenotypes not involving a clinical diagnosis.
None
See this image and copyright information in PMC

References

    1. Adams HHH, Hibar DP, Chouraki V, Stein JL, Nyquist PA, Rentería ME, Trompet S, Arias-Vasquez A, Seshadri S, Desrivières S, Beecham AH, Jahanshad N, Wittfeld K, Van der Lee SJ, Abramovic L, Alhusaini S, Amin N, Andersson M, Arfanakis K, Aribisala BS, Armstrong NJ, Athanasiu L, Axelsson T, Beiser A, Bernard M, Bis JC, Blanken LME, Blanton SH, Bohlken MM, Boks MP, Bralten J, Brickman AM, Carmichael O, Chakravarty MM, Chauhan G, Chen Q, Ching CRK, Cuellar-Partida G, Braber A.Den, Doan NT, Ehrlich S, Filippi I, Ge T, Giddaluru S, Goldman AL, Gottesman RF, Greven CU, Grimm O, Griswold ME, Guadalupe T, Hass J, Haukvik UK, Hilal S, Hofer E, Hoehn D, Holmes AJ, Hoogman M, Janowitz D, Jia T, Kasperaviciute D, Kim S, Klein M, Hoehn B, Lee PH, Liao J, Liewald DCM, Boks LM, Luciano M, Macare C, Marquand A, Matarin M, Mather KA, Mattheisen M, Mazoyer B, McKay DR, McWhirter R, Milaneschi Y, Mirza-Schreiber N, Muetzel RL, Maniega SM, Nho K, Nugent AC, Loohuis LMO, Oosterlaan J, Papmeyer M, Pappa I, Pirpamer L, Pudas S, Pütz B, Pirpamer KB, Ramasamy A, Richards JS, Risacher SL, Roiz-Santiañez R, Rommelse N, Rose EJ, Royle NA, Rundek T, Sämann PG, Satizabal CL, Schmaal L, Schork AJ, Shen L, Shin J, Shumskaya E, Smith AV, Sprooten E, Strike LT, Teumer A, Thomson R, Tordesillas-Gutierrez D, Toro R, Trabzuni D, Vaidya D, Van der Grond J, Van der Meer D, Van Donkelaar MMJ, Van Eijk KR, Van Erp TGM, Van Rooij D, Walton E, Westlye LT, Whelan CD, Windham BG, Winkler AM, Woldehawariat G, Wolf C, Wolfers T, Xu B, Yanek LR, Yang J, Zijdenbos A, Zwiers MP, Agartz I, Aggarwal NT, Almasy L, Ames D, Amouyel P, Andreassen OA, Arepalli S, Assareh AA, Barral S, Bastin ME, Becker DM, Becker JT, Bennett DA, Blangero J, van Bokhoven H, Boomsma DI, Brodaty H, Brouwer RM, Brunner HG, Buckner RL, Buitelaar JK, Bulayeva KB, Cahn W, Calhoun VD, Cannon DM, Cavalleri GL, Chen C, Cheng C-Y, Cichon S, Cookson MR, Corvin A, Crespo-Facorro B, Curran JE, Czisch M, Dale AM, Davies GE, De Geus EJC, De Jager PL, de Zubicaray GI, Delanty N, Depondt C, DeStefano AL, Dillman A, Djurovic S, Donohoe G, Drevets WC, Duggirala R, Dyer TD, Erk S, Espeseth T, Evans DA, Fedko IO, Fernández G, Ferrucci L, Fisher SE, Fleischman DA, Ford I, Foroud TM, Fox PT, Francks C, Fukunaga M, Gibbs JR, Glahn DC, Gollub RL, Göring HHH, Grabe HJ, Green RC, Gruber O, Gudnason V, Guelfi S, Hansell NK, Hardy J, Hartman CA, Hashimoto R, Hegenscheid K, Heinz A, Le Hellard S, Hernandez DG, Heslenfeld DJ, Ho B-C, Hoekstra PJ, Hoffmann W, Hofman A, Holsboer F, Homuth G, Hosten N, Hottenga J-J, Hulshoff Pol HE, Ikeda M, Ikram MK, Jack CR, Jenkinson M, Johnson R, Jönsson EG, Jukema JW, Kahn RS, Kanai R, Kloszewska I, Knopman DS, Kochunov P, Kwok JB, Lawrie SM, Jack H, Liu X, Longo DL, Longstreth WT, Lopez OL, Lovestone S, Martinez O, Martinot J-L, Mattay VS, McDonald C, McIntosh AM, McMahon KL, McMahon FJ, Mecocci P, Marquand I, Meyer-Lindenberg A, Drevets S, Montgomery GW, Morris DW, Mosley TH, Mühleisen TW, Müller-Myhsok B, Nalls MA, Nauck M, Nichols TE, Niessen WJ, Nöthen MM, Nyberg L, Ohi K, Olvera RL, Ophoff RA, Pandolfo M, Paus T, Pausova Z, Penninx BWJH, Pike GB, Potkin SG, Psaty BM, Reppermund S, Rietschel M, Roffman JL, Romanczuk-Seiferth N, Rotter JI, Ryten M, Sacco RL, Sachdev PS, Saykin AJ, Schmidt R, Schofield PR, Sigurdsson S, Simmons A, Singleton A, Sisodiya SM, Smith C, Smoller JW, Soininen H, Srikanth V, Steen VM, Stott DJ, Sussmann JE, Thalamuthu A, Tiemeier H, Toga AW, Traynor BJ, Troncoso J, Turner JA, Tzourio C, Uitterlinden AG, Hernández MCV, Van der Brug M, Van der Lugt A, Van der Wee NJA, Van Duijn CM, Van Haren NEM, Van ′t Ent D, Van Tol M-J, Vardarajan BN, Veltman DJ, Vernooij MW, Völzke H, Walter H, Wardlaw JM, Wassink TH, Weale ME, Weinberger DR, Weiner MW, Wen W, Westman E, White T, Beecham TY, Wright CB, Zielke HR, Zonderman AB, Deary IJ, DeCarli C, Schmidt H, Martin NG, De Craen AJM, Wright MJ, Launer LJ, Schumann G, Fornage M, Franke B, Debette S, Medland SE, Ikram MA, Rundek PM, 2016. Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat. Neurosci. 1569–1582. 10.1038/nn.4398. - DOI - PMC - PubMed
    1. Aguilar-Lacasaña S, Vilor-Tejedor N, Jansen PR, López-Vicente M, Bustamante M, Burgaleta M, Sunyer J, Alemany S, 2020. Polygenic risk for ADHD and ASD and their relation with cognitive measures in school children. Psychol. Med. 1–9. 10.1017/S0033291720003189. - DOI - PMC - PubMed
    1. Alemany S, Jansen PR, Muetzel RL, Marques N, El Marroun H, Jaddoe VWV, Polderman TJC, Tiemeier H, Posthuma D, White T, 2019. Common polygenic variations for psychiatric disorders and cognition in relation to brain morphology in the general pediatric population. J. Am. Acad. Child Adolesc. Psychiatry 58, 600–607. 10.1016/j.jaac.2018.09.443. - DOI - PubMed
    1. Allegrini AG, Cheesman R, Rimfeld K, Selzam S, Pingault J, Eley TC, Plomin R, 2020. The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence. J. Child Psychol. Psychiatry 61, 30–39. 10.1111/jcpp.13113. - DOI - PMC - PubMed
    1. Al-Mubarak BR, Omar A, Baz B, Al-Abdulaziz B, Magrashi AI, Al-Yemni E, Jabaan A, Monies D, Abouelhoda M, Abebe D, Ghaziuddin M, Al-Tassan NA, 2020. Whole exome sequencing in ADHD trios from single and multi-incident families implicates new candidate genes and highlights polygenic transmission. Eur. J. Hum. Genet. 28, 1098–1110. 10.1038/s41431-020-0619-7. - DOI - PMC - PubMed

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