Shared genetic background between children and adults with attention deficit/hyperactivity disorder


  • 1.

    Franke B, Michelini G, Asherson P, Banaschewski T, Bilbow A, Buitelaar JK, et al. Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan. Eur Neuropsychopharmacol. 2018;28:1059–88.

  • 2.

    Polanczyk GV, Salum GA, Sugaya LS, Caye A, Rohde LA. Annual research review: a meta-analysis of the worldwide prevalence of mental disorders in children and adolescents. J Child Psychol Psychiatry. 2015;56:345–65.

  • 3.

    Brikell I, Kuja-Halkola R, Larsson H. Heritability of attention-deficit hyperactivity disorder in adults. Am J Med Genet B Neuropsychiatr Genet. 2015;168:406–13.

  • 4.

    Kan KJ, Dolan CV, Nivard MG, Middeldorp CM, van Beijsterveldt CE, Willemsen G, et al. Genetic and environmental stability in attention problems across the lifespan: evidence from the Netherlands twin register. J Am Acad Child Adolesc Psychiatry. 2013;52:12–25.

  • 5.

    Kuntsi J, Rijsdijk F, Ronald A, Asherson P, Plomin R. Genetic influences on the stability of attention-deficit/hyperactivity disorder symptoms from early to middle childhood. Biol Psychiatry. 2005;57:647–54.

  • 6.

    Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat Genet. 2019;51:63–75.

  • 7.

    Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Mol Psychiatry. 2018.

  • 8.

    Ganna A, Satterstrom FK, Zekavat SM, Das I, Kurki MI, Churchhouse C, et al. Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum. Am J Hum Genet. 2018;102:1204–11.

  • 9.

    Martin J, O’Donovan MC, Thapar A, Langley K, Williams N. The relative contribution of common and rare genetic variants to ADHD. Transl Psychiatry. 2015;5:e506.

  • 10.

    Satterstrom FK, Walters RK, Singh T, Wigdor EM, Lescai F, Demontis D, et al. ASD and ADHD have a similar burden of rare protein-truncating variants. (2018).

  • 11.

    Hawi Z, Cummins TD, Tong J, Arcos-Burgos M, Zhao Q, Matthews N, et al. Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: a next-generation sequencing study. Mol Psychiatry. 2017;22:580–84.

  • 12.

    Brainstorm C, Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, et al. Analysis of shared heritability in common disorders of the brain. Science. 2018;360.

  • 13.

    Shaw P, Stringaris A, Nigg J, Leibenluft E. Emotion dysregulation in attention deficit hyperactivity disorder. Am J Psychiatry. 2014;171:276–93.

  • 14.

    Wilens TE, Biederman J, Faraone SV, Martelon M, Westerberg D, Spencer TJ. Presenting ADHD symptoms, subtypes, and comorbid disorders in clinically referred adults with ADHD. J Clin Psychiatry. 2009;70:1557–62.

  • 15.

    Anker E, Bendiksen B, Heir T. Comorbid psychiatric disorders in a clinical sample of adults with ADHD, and associations with education, work and social characteristics: a cross-sectional study. BMJ Open. 2018;8:e019700.

  • 16.

    Biederman J, Faraone SV, Spencer T, Wilens T, Norman D, Lapey KA, et al. Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1993;150:1792–8.

  • 17.

    Kessler RC, Adler LA, Barkley R, Biederman J, Conners CK, Faraone SV, et al. Patterns and predictors of attention-deficit/hyperactivity disorder persistence into adulthood: results from the national comorbidity survey replication. Biol Psychiatry. 2005;57:1442–51.

  • 18.

    Larson K, Russ SA, Kahn RS, Halfon N. Patterns of comorbidity, functioning, and service use for US children with ADHD, 2007. Pediatrics. 2011;127:462–70.

  • 19.

    Dalsgaard S, Østergaard SD, Leckman JF, Mortensen PB, Pedersen MG. Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study. Lancet. 2015;385:2190–96.

  • 20.

    Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Prim. 2015;1:15020.

  • 21.

    Kupper T, Haavik J, Drexler H, Ramos-Quiroga JA, Wermelskirchen D, Prutz C, et al. The negative impact of attention-deficit/hyperactivity disorder on occupational health in adults and adolescents. Int Arch Occup Environ Health. 2012;85:837–47.

  • 22.

    Voigt RG, Katusic SK, Colligan RC, Killian JM, Weaver AL, Barbaresi WJ. Academic achievement in adults with a history of childhood attention-deficit/hyperactivity disorder: a population-based prospective study. J Dev Behav Pediatr. 2017;38:1–11.

  • 23.

    Strine TW, Lesesne CA, Okoro CA, McGuire LC, Chapman DP, Balluz LS, et al. Emotional and behavioral difficulties and impairments in everyday functioning among children with a history of attention-deficit/hyperactivity disorder. Prev Chronic Dis. 2006;3:A52.

  • 24.

    Biederman J, Petty CR, Evans M, Small J, Faraone SV. How persistent is ADHD? A controlled 10-year follow-up study of boys with ADHD. Psychiatry Res. 2010;177:299–304.

  • 25.

    Caye A, Spadini AV, Karam RG, Grevet EH, Rovaris DL, Bau CH, et al. Predictors of persistence of ADHD into adulthood: a systematic review of the literature and meta-analysis. Eur Child Adolesc Psychiatry. 2016;25:1151–59.

  • 26.

    Cheung CH, Rijdijk F, McLoughlin G, Faraone SV, Asherson P, Kuntsi J. Childhood predictors of adolescent and young adult outcome in ADHD. J Psychiatr Res. 2015;62:92–100.

  • 27.

    Riglin L, Collishaw S, Thapar AK, Dalsgaard S, Langley K, Smith GD, et al. Association of genetic risk variants with attention-deficit/hyperactivity disorder trajectories in the general population. JAMA Psychiatry. 2016;73:1285–92.

  • 28.

    Roy A, Hechtman L, Arnold LE, Swanson JM, Molina BSG, Sibley MH, et al. Childhood predictors of adult functional outcomes in the multimodal treatment study of attention-deficit/hyperactivity disorder (MTA). J Am Acad Child Adolesc Psychiatry. 2017;56:687–95. e7

  • 29.

    Pingault JB, Viding E, Galera C, Greven CU, Zheng Y, Plomin R, et al. Genetic and environmental influences on the developmental course of attention-deficit/hyperactivity disorder symptoms from childhood to adolescence. JAMA Psychiatry. 2015;72:651–8.

  • 30.

    Rietveld MJ, Hudziak JJ, Bartels M, van Beijsterveldt CE, Boomsma DI. Heritability of attention problems in children: longitudinal results from a study of twins, age 3 to 12. J Child Psychol Psychiatry. 2004;45:577–88.

  • 31.

    Akutagava-Martins GC, Salatino-Oliveira A, Kieling C, Genro JP, Polanczyk GV, Anselmi L, et al. COMT and DAT1 genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect. J Psychiatry Neurosci. 2016;41:405–12.

  • 32.

    Bonvicini C, Faraone SV, Scassellati C. Attention-deficit hyperactivity disorder in adults: a systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies. Mol Psychiatry. 2016;21:1643.

  • 33.

    Bonvicini C, Faraone SV, Scassellati C. Common and specific genes and peripheral biomarkers in children and adults with attention-deficit/hyperactivity disorder. World J Biol Psychiatry. 2018;19:80–100.

  • 34.

    Johansson S, Halleland H, Halmoy A, Jacobsen KK, Landaas ET, Dramsdahl M, et al. Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1470–5.

  • 35.

    Lesch KP, Timmesfeld N, Renner TJ, Halperin R, Roser C, Nguyen TT, et al. Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm. 2008;115:1573–85.

  • 36.

    Ribases M, Ramos-Quiroga JA, Hervas A, Bosch R, Bielsa A, Gastaminza X, et al. Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry. 2009;14:71–85.

  • 37.

    Sanchez-Mora C, Ramos-Quiroga JA, Bosch R, Corrales M, Garcia-Martinez I, Nogueira M, et al. Case-control genome-wide association study of persistent attention-deficit hyperactivity disorder identifies FBXO33 as a novel susceptibility gene for the disorder. Neuropsychopharmacology. 2015;40:915–26.

  • 38.

    Thissen AJ, Bralten J, Rommelse NN, Arias-Vasquez A, Greven CU, Heslenfeld D, et al. The role of age in association analyses of ADHD and related neurocognitive functioning: A proof of concept for dopaminergic and serotonergic genes. Am J Med Genet B Neuropsychiatr Genet. 2015;168:471–79.

  • 39.

    Zayats T, Athanasiu L, Sonderby I, Djurovic S, Westlye LT, Tamnes CK, et al. Genome-wide analysis of attention deficit hyperactivity disorder in Norway. PLoS One. 2015;10:e0122501.

  • 40.

    Neale BM, Medland SE, Ripke S, Asherson P, Franke B, Lesch KP, et al. Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010;49:884–97.

  • 41.

    Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009;5:e1000529.

  • 42.

    Li Y, Willer C, Sanna S, Abecasis G. Genotype imputation. Annu Rev Genomics Hum Genet. 2009;10:387–406.

  • 43.

    Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol. 2010;34:816–34.

  • 44.

    Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.

  • 45.

    Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26:2190–1.

  • 46.

    Winkler TW, Day FR, Croteau-Chonka DC, Wood AR, Locke AE, Magi R, et al. Quality control and conduct of genome-wide association meta-analyses. Nat Protoc. 2014;9:1192–212.

  • 47.

    Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics. 2010;26:2336–7.

  • 48.

    Bulik-Sullivan BK, Loh PR, Finucane HK, Ripke S, Yang J, Schizophrenia Working Group of the Psychiatric Genomics C. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet. 2015;47:291–5.

  • 49.

    Finucane HK, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y, Loh PR, et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat Genet. 2015;47:1228–35.

  • 50.

    de Leeuw CA, Mooij JM, Heskes T, Posthuma D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol. 2015;11:e1004219.

  • 51.

    Han B, Pouget JG, Slowikowski K, Stahl E, Lee CH, Diogo D, et al. A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases. Nat Genet. 2016;48:803–10.

  • 52.

    Middeldorp CM, Hammerschlag AR, Ouwens KG, Groen-Blokhuis MM, Pourcain BS, Greven CU, et al. A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts. J Am Acad Child Adolesc Psychiatry. 2016;55:896–905. e6

  • 53.

    Zheng J, Erzurumluoglu AM, Elsworth BL, Kemp JP, Howe L, Haycock PC, et al. LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics. 2017;33:272–79.

  • 54.

    Westra HJ, Peters MJ, Esko T, Yaghootkar H, Schurmann C, Kettunen J, et al. Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat Genet. 2013;45:1238–43.

  • 55.

    Qi T, Wu Y, Zeng J, Zhang F, Xue A, Jiang L, et al. Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood. Nat Commun. 2018;9:2282.

  • 56.

    Chen Q, Brikell I, Lichtenstein P, Serlachius E, Kuja-Halkola R, Sandin S, et al. Familial aggregation of attention-deficit/hyperactivity disorder. J Child Psychol Psychiatry. 2017;58:231–39.

  • 57.

    Biederman J, Faraone SV, Mick E, Spencer T, Wilens T, Kiely K, et al. High risk for attention deficit hyperactivity disorder among children of parents with childhood onset of the disorder: a pilot study. Am J Psychiatry. 1995;152:431–5.

  • 58.

    Chapman NH, Nato AQ Jr., Bernier R, Ankenman K, Sohi H, Munson J, et al. Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes. Hum Genet. 2015;134:1055–68.

  • 59.

    Shimizu T, Hibi M. Formation and patterning of the forebrain and olfactory system by zinc-finger genes Fezf1 and Fezf2. Dev Growth Differ. 2009;51:221–31.

  • 60.

    Koukoulas I, Augustine C, Silkenbeumer N, Gunnersen JM, Scott HS, Tan SS. Genomic organisation and nervous system expression of radial spoke protein 3. Gene. 2004;336:15–23.

  • 61.

    Bonora E, Graziano C, Minopoli F, Bacchelli E, Magini P, Diquigiovanni C, et al. Maternally inherited genetic variants of CADPS2 are present in autism spectrum disorders and intellectual disability patients. EMBO Mol Med. 2014;6:795–809.

  • 62.

    Hattori K, Tanaka H, Wakabayashi C, Yamamoto N, Uchiyama H, Teraishi T, et al. Expression of Ca(2)(+)-dependent activator protein for secretion 2 is increased in the brains of schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1738–43.

  • 63.

    Sadakata T, Shinoda Y, Ishizaki Y, Furuichi T. Analysis of gene expression in Ca(2+)-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways. Neurosci Lett. 2017;639:88–93.

  • 64.

    Velez JI, Chandrasekharappa SC, Henao E, Martinez AF, Harper U, Jones M, et al. Pooling/bootstrap-based GWAS (pbGWAS) identifies new loci modifying the age of onset in PSEN1 p.Glu280Ala Alzheimer’s disease. Mol Psychiatry. 2013;18:568–75.

  • 65.

    Fyfe JC, Madsen M, Hojrup P, Christensen EI, Tanner SM, de la Chapelle A, et al. The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood. 2004;103:1573–9.

  • 66.

    Tanner SM, Aminoff M, Wright FA, Liyanarachchi S, Kuronen M, Saarinen A, et al. Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia. Nat Genet. 2003;33:426–9.

  • 67.

    Venkatramanan S, Armata IE, Strupp BJ, Finkelstein JL. Vitamin B-12 and cognition in children. Adv Nutr. 2016;7:879–88.

  • 68.

    Savage JE, Jansen PR, Stringer S, Watanabe K, Bryois J, de Leeuw CA, et al. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat Genet. 2018;50:912–19.

  • Source link


    Please enter your comment!
    Please enter your name here