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Published in: ADHD Attention Deficit and Hyperactivity Disorders 3/2010

01-11-2010 | Review Article

Toward a better understanding of ADHD: LPHN3 gene variants and the susceptibility to develop ADHD

Authors: Mauricio Arcos-Burgos, Maximilian Muenke

Published in: ADHD Attention Deficit and Hyperactivity Disorders | Issue 3/2010

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Abstract

During the past 15 years, an impressive amount of genetic information has become available in the research field of psychiatry, particularly as it relates to attention-deficit/hyperactivity disorder (ADHD). However, the classical clinical approach to ADHD has minimally affected and not significantly been improved by this genetic revolution. It is difficult to predict how long it will take for genetic findings to alter the way clinicians treat patients with ADHD. New medications or treatment protocols may take years to become routine clinical practice. However, when taken together, recent successes in genomics, pharmacogenomics, and genetic epidemiology have the potential (1) to prevent comorbid consequences of ADHD, (2) to individualize therapies for patients with ADHD, and (3) to define new epidemiological policies to aid with the impact of ADHD on society. Here, we present an overview of how genetic research may affect and improve the quality of life of patients with ADHD: as an example, we use the discovery of LPHN3, a new gene in which variants have recently been shown to be associated with ADHD.
Literature
go back to reference Acosta MT, Arcos-Burgos M, Muenke M (2004) Attention deficit/hyperactivity disorder (ADHD): complex phenotype, simple genotype? Genet Med 6(1):1–15CrossRefPubMed Acosta MT, Arcos-Burgos M, Muenke M (2004) Attention deficit/hyperactivity disorder (ADHD): complex phenotype, simple genotype? Genet Med 6(1):1–15CrossRefPubMed
go back to reference Arcos-Burgos M, Acosta MT (2007) Tuning major gene variants conditioning human behavior: the anachronism of ADHD. Curr Opin Genet Dev 17(3):234–238CrossRefPubMed Arcos-Burgos M, Acosta MT (2007) Tuning major gene variants conditioning human behavior: the anachronism of ADHD. Curr Opin Genet Dev 17(3):234–238CrossRefPubMed
go back to reference Arcos-Burgos M, Castellanos FX, Lopera F, Pineda D, Palacio JD, Garcia M et al (2002) Attention-deficit/hyperactivity disorder (ADHD): feasibility of linkage analysis in a genetic isolate using extended and multigenerational pedigrees. Clin Genet 61(5):335–343CrossRefPubMed Arcos-Burgos M, Castellanos FX, Lopera F, Pineda D, Palacio JD, Garcia M et al (2002) Attention-deficit/hyperactivity disorder (ADHD): feasibility of linkage analysis in a genetic isolate using extended and multigenerational pedigrees. Clin Genet 61(5):335–343CrossRefPubMed
go back to reference Arcos-Burgos M, Castellanos FX, Konecki D, Lopera F, Pineda D, Palacio JD et al (2004a) Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate. Mol Psychiatry 9(3):252–259CrossRefPubMed Arcos-Burgos M, Castellanos FX, Konecki D, Lopera F, Pineda D, Palacio JD et al (2004a) Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate. Mol Psychiatry 9(3):252–259CrossRefPubMed
go back to reference Arcos-Burgos M, Castellanos FX, Pineda D, Lopera F, Palacio JD, Palacio LG et al (2004b) Attention-deficit/hyperactivity disorder in a population isolate: linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11. Am J Hum Genet 75(6):998–1014CrossRefPubMed Arcos-Burgos M, Castellanos FX, Pineda D, Lopera F, Palacio JD, Palacio LG et al (2004b) Attention-deficit/hyperactivity disorder in a population isolate: linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11. Am J Hum Genet 75(6):998–1014CrossRefPubMed
go back to reference Arcos-Burgos M, Jain M, Acosta MT, Shively S, Stanescu H, Wallis D et al. (2010) A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol Psychiatry (in press) Arcos-Burgos M, Jain M, Acosta MT, Shively S, Stanescu H, Wallis D et al. (2010) A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol Psychiatry (in press)
go back to reference Banerjee E, Sinha S, Chatterjee A, Gangopadhyay PK, Singh M, Nandagopal K (2006) A family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD). Am J Med Genet B Neuropsychiatr Genet 141B(4):361–366CrossRefPubMed Banerjee E, Sinha S, Chatterjee A, Gangopadhyay PK, Singh M, Nandagopal K (2006) A family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD). Am J Med Genet B Neuropsychiatr Genet 141B(4):361–366CrossRefPubMed
go back to reference Biederman J, Faraone SV, Keenan K, Benjamin J, Krifcher B, Moore C et al (1992) Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples. Arch Gen Psychiatry 49(9):728–738PubMed Biederman J, Faraone SV, Keenan K, Benjamin J, Krifcher B, Moore C et al (1992) Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples. Arch Gen Psychiatry 49(9):728–738PubMed
go back to reference Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N et al (2006) The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry 11(10):934–953CrossRefPubMed Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N et al (2006) The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry 11(10):934–953CrossRefPubMed
go back to reference Cadieu E, Neff MW, Quignon P, Walsh K, Chase K, Parker HG et al (2009) Coat variation in the domestic dog is governed by variants in three genes. Science 326(5949):150–153CrossRefPubMed Cadieu E, Neff MW, Quignon P, Walsh K, Chase K, Parker HG et al (2009) Coat variation in the domestic dog is governed by variants in three genes. Science 326(5949):150–153CrossRefPubMed
go back to reference Carvajal-Carmona LG, Ophoff R, Service S, Hartiala J, Molina J, Leon P et al (2003) Genetic demography of Antioquia (Colombia) and the Central Valley of Costa Rica. Hum Genet 112(5–6):534–541PubMed Carvajal-Carmona LG, Ophoff R, Service S, Hartiala J, Molina J, Leon P et al (2003) Genetic demography of Antioquia (Colombia) and the Central Valley of Costa Rica. Hum Genet 112(5–6):534–541PubMed
go back to reference Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P et al (2009) Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 106(45):19096–19101CrossRefPubMed Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P et al (2009) Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 106(45):19096–19101CrossRefPubMed
go back to reference Coghill D, Banaschewski T (2009) The genetics of attention-deficit/hyperactivity disorder. Expert Rev Neurother 9(10):1547–1565CrossRefPubMed Coghill D, Banaschewski T (2009) The genetics of attention-deficit/hyperactivity disorder. Expert Rev Neurother 9(10):1547–1565CrossRefPubMed
go back to reference Collins FS, Manolio TA (2007) Merging and emerging cohorts: necessary but not sufficient. Nature 445(7125):259CrossRefPubMed Collins FS, Manolio TA (2007) Merging and emerging cohorts: necessary but not sufficient. Nature 445(7125):259CrossRefPubMed
go back to reference Comings DE, Chen C, Wu S, Muhleman D (1999) Association of the androgen receptor gene (AR) with ADHD and conduct disorder. Neuroreport 10(7):1589–1592CrossRefPubMed Comings DE, Chen C, Wu S, Muhleman D (1999) Association of the androgen receptor gene (AR) with ADHD and conduct disorder. Neuroreport 10(7):1589–1592CrossRefPubMed
go back to reference Durrant C, Morris AP (2005) Linkage disequilibrium mapping via cladistic analysis of phase-unknown genotypes and inferred haplotypes in the Genetic Analysis Workshop 14 simulated data. BMC Genet 6(Suppl 1):S100CrossRefPubMed Durrant C, Morris AP (2005) Linkage disequilibrium mapping via cladistic analysis of phase-unknown genotypes and inferred haplotypes in the Genetic Analysis Workshop 14 simulated data. BMC Genet 6(Suppl 1):S100CrossRefPubMed
go back to reference Durrant C, Zondervan KT, Cardon LR, Hunt S, Deloukas P, Morris AP (2004) Linkage disequilibrium mapping via cladistic analysis of single-nucleotide polymorphism haplotypes. Am J Hum Genet 75(1):35–43CrossRefPubMed Durrant C, Zondervan KT, Cardon LR, Hunt S, Deloukas P, Morris AP (2004) Linkage disequilibrium mapping via cladistic analysis of single-nucleotide polymorphism haplotypes. Am J Hum Genet 75(1):35–43CrossRefPubMed
go back to reference Elia J, Capasso M, Zaheer Z, Lantieri F, Ambrosini P, Berrettini W et al (2009) Candidate gene analysis in an on-going genome-wide association study of attention-deficit hyperactivity disorder: suggestive association signals in ADRA1A. Psychiatr Genet 19(3):134–141CrossRefPubMed Elia J, Capasso M, Zaheer Z, Lantieri F, Ambrosini P, Berrettini W et al (2009) Candidate gene analysis in an on-going genome-wide association study of attention-deficit hyperactivity disorder: suggestive association signals in ADRA1A. Psychiatr Genet 19(3):134–141CrossRefPubMed
go back to reference Elston RC, Yelverton KC (1975) General models for segregation analysis. Am J Hum Genet 27(1):31–45PubMed Elston RC, Yelverton KC (1975) General models for segregation analysis. Am J Hum Genet 27(1):31–45PubMed
go back to reference Faraone SV, Mick E (2010) Molecular genetics of attention deficit hyperactivity disorder. Psychiatr Clin North Am 33(1):159–180CrossRefPubMed Faraone SV, Mick E (2010) Molecular genetics of attention deficit hyperactivity disorder. Psychiatr Clin North Am 33(1):159–180CrossRefPubMed
go back to reference Faraone SV, Biederman J, Weiffenbach B, Keith T, Chu MP, Weaver A et al (1999) Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder. Am J Psychiatry 156(5):768–770PubMed Faraone SV, Biederman J, Weiffenbach B, Keith T, Chu MP, Weaver A et al (1999) Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder. Am J Psychiatry 156(5):768–770PubMed
go back to reference Faraone SV, Biederman J, Monuteaux MC (2000) Toward guidelines for pedigree selection in genetic studies of attention deficit hyperactivity disorder. Genet Epidemiol 18(1):1–16CrossRefPubMed Faraone SV, Biederman J, Monuteaux MC (2000) Toward guidelines for pedigree selection in genetic studies of attention deficit hyperactivity disorder. Genet Epidemiol 18(1):1–16CrossRefPubMed
go back to reference Faraone SV, Doyle AE, Mick E, Biederman J (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 158(7):1052–1057CrossRefPubMed Faraone SV, Doyle AE, Mick E, Biederman J (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 158(7):1052–1057CrossRefPubMed
go back to reference Franke B, Neale BM, Faraone SV (2009) Genome-wide association studies in ADHD. Hum Genet 126(1):13–50CrossRefPubMed Franke B, Neale BM, Faraone SV (2009) Genome-wide association studies in ADHD. Hum Genet 126(1):13–50CrossRefPubMed
go back to reference Friedel S, Saar K, Sauer S, Dempfle A, Walitza S, Renner T et al (2007) Association and linkage of allelic variants of the dopamine transporter gene in ADHD. Mol Psychiatry 12(10):923–933CrossRefPubMed Friedel S, Saar K, Sauer S, Dempfle A, Walitza S, Renner T et al (2007) Association and linkage of allelic variants of the dopamine transporter gene in ADHD. Mol Psychiatry 12(10):923–933CrossRefPubMed
go back to reference Gizer IR, Ficks C, Waldman ID (2009) Candidate gene studies of ADHD: a meta-analytic review. Hum Genet 126(1):51–90CrossRefPubMed Gizer IR, Ficks C, Waldman ID (2009) Candidate gene studies of ADHD: a meta-analytic review. Hum Genet 126(1):51–90CrossRefPubMed
go back to reference Guo X, Elston RC (2000) Two-stage global search designs for linkage analysis II: including discordant relative pairs in the study. Genet Epidemiol 18(2):111–127CrossRefPubMed Guo X, Elston RC (2000) Two-stage global search designs for linkage analysis II: including discordant relative pairs in the study. Genet Epidemiol 18(2):111–127CrossRefPubMed
go back to reference Hildebrandt M, Bender R, Gehrmann U, Blettner M (2006) Calculating confidence intervals for impact numbers. BMC Med Res Methodol 6:32CrossRefPubMed Hildebrandt M, Bender R, Gehrmann U, Blettner M (2006) Calculating confidence intervals for impact numbers. BMC Med Res Methodol 6:32CrossRefPubMed
go back to reference Ichtchenko K, Khvotchev M, Kiyatkin N, Simpson L, Sugita S, Sudhof TC (1998) alpha-latrotoxin action probed with recombinant toxin: receptors recruit alpha-latrotoxin but do not transduce an exocytotic signal. EMBO J 17(21):6188–6199CrossRefPubMed Ichtchenko K, Khvotchev M, Kiyatkin N, Simpson L, Sugita S, Sudhof TC (1998) alpha-latrotoxin action probed with recombinant toxin: receptors recruit alpha-latrotoxin but do not transduce an exocytotic signal. EMBO J 17(21):6188–6199CrossRefPubMed
go back to reference Iyengar SK, Song D, Klein BE, Klein R, Schick JH, Humphrey J et al (2004) Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration. Am J Hum Genet 74(1):20–39CrossRefPubMed Iyengar SK, Song D, Klein BE, Klein R, Schick JH, Humphrey J et al (2004) Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration. Am J Hum Genet 74(1):20–39CrossRefPubMed
go back to reference Jain M, Palacio LG, Castellanos FX, Palacio JD, Pineda D, Restrepo MI et al (2007) Attention-deficit/hyperactivity disorder and comorbid disruptive behavior disorders: evidence of pleiotropy and new susceptibility loci. Biol Psychiatry 61(12):1329–1339CrossRefPubMed Jain M, Palacio LG, Castellanos FX, Palacio JD, Pineda D, Restrepo MI et al (2007) Attention-deficit/hyperactivity disorder and comorbid disruptive behavior disorders: evidence of pleiotropy and new susceptibility loci. Biol Psychiatry 61(12):1329–1339CrossRefPubMed
go back to reference Kent L, Doerry U, Hardy E, Parmar R, Gingell K, Hawi Z et al (2002) Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis. Mol Psychiatry 7(8):908–912CrossRefPubMed Kent L, Doerry U, Hardy E, Parmar R, Gingell K, Hawi Z et al (2002) Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis. Mol Psychiatry 7(8):908–912CrossRefPubMed
go back to reference Kent L, Green E, Hawi Z, Kirley A, Dudbridge F, Lowe N et al (2005) Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD. Mol Psychiatry 10(10):939–943CrossRefPubMed Kent L, Green E, Hawi Z, Kirley A, Dudbridge F, Lowe N et al (2005) Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD. Mol Psychiatry 10(10):939–943CrossRefPubMed
go back to reference Kieling C, Goncalves RR, Tannock R, Castellanos FX (2008) Neurobiology of attention deficit hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 17(2):285–307, viiiCrossRefPubMed Kieling C, Goncalves RR, Tannock R, Castellanos FX (2008) Neurobiology of attention deficit hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 17(2):285–307, viiiCrossRefPubMed
go back to reference Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921CrossRefPubMed Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921CrossRefPubMed
go back to reference Lee SS, Lahey BB, Waldman I, Van Hulle CA, Rathouz P, Pelham WE et al (2007) Association of dopamine transporter genotype with disruptive behavior disorders in an eight-year longitudinal study of children and adolescents. Am J Med Genet B Neuropsychiatr Genet 144B(3):310–317CrossRefPubMed Lee SS, Lahey BB, Waldman I, Van Hulle CA, Rathouz P, Pelham WE et al (2007) Association of dopamine transporter genotype with disruptive behavior disorders in an eight-year longitudinal study of children and adolescents. Am J Med Genet B Neuropsychiatr Genet 144B(3):310–317CrossRefPubMed
go back to reference Lelianova VG, Davletov BA, Sterling A, Rahman MA, Grishin EV, Totty NF et al (1997) Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J Biol Chem 272(34):21504–21508CrossRefPubMed Lelianova VG, Davletov BA, Sterling A, Rahman MA, Grishin EV, Totty NF et al (1997) Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J Biol Chem 272(34):21504–21508CrossRefPubMed
go back to reference Lesch KP, Timmesfeld N, Renner TJ, Halperin R, Roser C, Nguyen TT et al (2008) Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm 115(11):1573–1585CrossRefPubMed Lesch KP, Timmesfeld N, Renner TJ, Halperin R, Roser C, Nguyen TT et al (2008) Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm 115(11):1573–1585CrossRefPubMed
go back to reference Li D, Sham PC, Owen MJ, He L (2006) Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum Mol Genet 15(14):2276–2284CrossRefPubMed Li D, Sham PC, Owen MJ, He L (2006) Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum Mol Genet 15(14):2276–2284CrossRefPubMed
go back to reference Linets’ka MV, Storchak LH, Himmelreich NH (2002) Effect of synaptosomal cytosolic [3H]GABA pool depletion on secretory ability of alpha-latrotoxin. Ukr Biokhim Zh 74(3):65–72PubMed Linets’ka MV, Storchak LH, Himmelreich NH (2002) Effect of synaptosomal cytosolic [3H]GABA pool depletion on secretory ability of alpha-latrotoxin. Ukr Biokhim Zh 74(3):65–72PubMed
go back to reference Lopera F, Palacio LG, Jimenez I, Villegas P, Puerta IC, Pineda D et al (1999) Discrimination between genetic factors in attention deficit. Rev Neurol 28(7):660–664PubMed Lopera F, Palacio LG, Jimenez I, Villegas P, Puerta IC, Pineda D et al (1999) Discrimination between genetic factors in attention deficit. Rev Neurol 28(7):660–664PubMed
go back to reference Lowe N, Kirley A, Hawi Z, Sham P, Wickham H, Kratochvil CJ et al (2004) Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes. Am J Hum Genet 74(2):348–356CrossRefPubMed Lowe N, Kirley A, Hawi Z, Sham P, Wickham H, Kratochvil CJ et al (2004) Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes. Am J Hum Genet 74(2):348–356CrossRefPubMed
go back to reference Maher BS, Marazita ML, Moss HB, Vanyukov MM (1999) Segregation analysis of attention deficit hyperactivity disorder. Am J Med Genet 88(1):71–78CrossRefPubMed Maher BS, Marazita ML, Moss HB, Vanyukov MM (1999) Segregation analysis of attention deficit hyperactivity disorder. Am J Med Genet 88(1):71–78CrossRefPubMed
go back to reference Maher BS, Marazita ML, Ferrell RE, Vanyukov MM (2002) Dopamine system genes and attention deficit hyperactivity disorder: a meta-analysis. Psychiatr Genet 12(4):207–215CrossRefPubMed Maher BS, Marazita ML, Ferrell RE, Vanyukov MM (2002) Dopamine system genes and attention deficit hyperactivity disorder: a meta-analysis. Psychiatr Genet 12(4):207–215CrossRefPubMed
go back to reference Manolio TA, Collins FS (2009) The HapMap and genome-wide association studies in diagnosis and therapy. Annu Rev Med 60:443–456CrossRefPubMed Manolio TA, Collins FS (2009) The HapMap and genome-wide association studies in diagnosis and therapy. Annu Rev Med 60:443–456CrossRefPubMed
go back to reference Manolio TA, Rodriguez LL, Brooks L, Abecasis G, Ballinger D, Daly M et al (2007) New models of collaboration in genome-wide association studies: the Genetic Association Information Network. Nat Genet 39(9):1045–1051CrossRefPubMed Manolio TA, Rodriguez LL, Brooks L, Abecasis G, Ballinger D, Daly M et al (2007) New models of collaboration in genome-wide association studies: the Genetic Association Information Network. Nat Genet 39(9):1045–1051CrossRefPubMed
go back to reference Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ et al (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753CrossRefPubMed Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ et al (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753CrossRefPubMed
go back to reference Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M et al (2002) Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA). Mol Psychiatry 7(6):626–632CrossRefPubMed Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M et al (2002) Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA). Mol Psychiatry 7(6):626–632CrossRefPubMed
go back to reference Marazita ML, Elston RC, Namboodiri KK, Hames CG (1983) Factors contributing to the variability in serum lipid levels and blood pressure in a large kindred. Am J Epidemiol 118(6):806–817PubMed Marazita ML, Elston RC, Namboodiri KK, Hames CG (1983) Factors contributing to the variability in serum lipid levels and blood pressure in a large kindred. Am J Epidemiol 118(6):806–817PubMed
go back to reference Marazita ML, Spence MA, Melnick M (1984) Genetic analysis of cleft lip with or without cleft palate in Danish kindreds. Am J Med Genet 19(1):9–18CrossRefPubMed Marazita ML, Spence MA, Melnick M (1984) Genetic analysis of cleft lip with or without cleft palate in Danish kindreds. Am J Med Genet 19(1):9–18CrossRefPubMed
go back to reference Marazita ML, Spence MA, Melnick M (1986) Major gene determination of liability to cleft lip with or without cleft palate: a multiracial view. J Craniofac Genet Dev Biol Suppl 2:89–97PubMed Marazita ML, Spence MA, Melnick M (1986) Major gene determination of liability to cleft lip with or without cleft palate: a multiracial view. J Craniofac Genet Dev Biol Suppl 2:89–97PubMed
go back to reference Martin ER, Monks SA, Warren LL, Kaplan NL (2000) A test for linkage and association in general pedigrees: the pedigree disequilibrium test. Am J Hum Genet 67(1):146–154CrossRefPubMed Martin ER, Monks SA, Warren LL, Kaplan NL (2000) A test for linkage and association in general pedigrees: the pedigree disequilibrium test. Am J Hum Genet 67(1):146–154CrossRefPubMed
go back to reference Matsushita H, Lelianova VG, Ushkaryov YA (1999) The latrophilin family: multiply spliced G protein-coupled receptors with differential tissue distribution. FEBS Lett 443(3):348–352CrossRefPubMed Matsushita H, Lelianova VG, Ushkaryov YA (1999) The latrophilin family: multiply spliced G protein-coupled receptors with differential tissue distribution. FEBS Lett 443(3):348–352CrossRefPubMed
go back to reference Mee CJ, Tomlinson SR, Perestenko PV, De Pomerai D, Duce IR, Usherwood PN et al (2004) Latrophilin is required for toxicity of black widow spider venom in Caenorhabditis elegans. Biochem J 378(Pt 1):185–191CrossRefPubMed Mee CJ, Tomlinson SR, Perestenko PV, De Pomerai D, Duce IR, Usherwood PN et al (2004) Latrophilin is required for toxicity of black widow spider venom in Caenorhabditis elegans. Biochem J 378(Pt 1):185–191CrossRefPubMed
go back to reference Neuman RJ, Heath A, Reich W, Bucholz KK, Madden PAF, Sun L et al (2001) Latent class analysis of ADHD and comorbid symptoms in a population sample of adolescent female twins. J Child Psychol Psychiatry 42(7):933–942CrossRefPubMed Neuman RJ, Heath A, Reich W, Bucholz KK, Madden PAF, Sun L et al (2001) Latent class analysis of ADHD and comorbid symptoms in a population sample of adolescent female twins. J Child Psychol Psychiatry 42(7):933–942CrossRefPubMed
go back to reference Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C et al (2009) Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461(7261):272–276CrossRefPubMed Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C et al (2009) Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461(7261):272–276CrossRefPubMed
go back to reference Palacio JD, Castellanos FX, Pineda DA, Lopera F, Arcos-Burgos M, Quiroz YT et al (2004) Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families. J Am Acad Child Adolesc Psychiatry 43(12):1506–1515CrossRefPubMed Palacio JD, Castellanos FX, Pineda DA, Lopera F, Arcos-Burgos M, Quiroz YT et al (2004) Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families. J Am Acad Child Adolesc Psychiatry 43(12):1506–1515CrossRefPubMed
go back to reference Pineda DA, Palacio LG, Puerta IC, Merchan V, Arango CP, Galvis AY et al (2007) Environmental influences that affect attention deficit/hyperactivity disorder: study of a genetic isolate. Eur Child Adolesc Psychiatry 16(5):337–346CrossRefPubMed Pineda DA, Palacio LG, Puerta IC, Merchan V, Arango CP, Galvis AY et al (2007) Environmental influences that affect attention deficit/hyperactivity disorder: study of a genetic isolate. Eur Child Adolesc Psychiatry 16(5):337–346CrossRefPubMed
go back to reference Rasmussen ER, Neuman RJ, Heath AC, Levy F, Hay DA, Todd RD (2002) Replication of the latent class structure of attention-deficit/hyperactivity disorder (ADHD) subtypes in a sample of Australian twins. J Child Psychol Psychiatry 43(8):1018–1028CrossRefPubMed Rasmussen ER, Neuman RJ, Heath AC, Levy F, Hay DA, Todd RD (2002) Replication of the latent class structure of attention-deficit/hyperactivity disorder (ADHD) subtypes in a sample of Australian twins. J Child Psychol Psychiatry 43(8):1018–1028CrossRefPubMed
go back to reference Reiersen AM, Constantino JN, Grimmer M, Martin NG, Todd RD (2008) Evidence for shared genetic influences on self-reported ADHD and autistic symptoms in young adult Australian twins. Twin Res Hum Genet 11(6):579–585CrossRefPubMed Reiersen AM, Constantino JN, Grimmer M, Martin NG, Todd RD (2008) Evidence for shared genetic influences on self-reported ADHD and autistic symptoms in young adult Australian twins. Twin Res Hum Genet 11(6):579–585CrossRefPubMed
go back to reference Ribases M, Ramos-Quiroga JA, Hervas A, Bosch R, Bielsa A, Gastaminza X et al (2009) Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry 14(1):71–85CrossRefPubMed Ribases M, Ramos-Quiroga JA, Hervas A, Bosch R, Bielsa A, Gastaminza X et al (2009) Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry 14(1):71–85CrossRefPubMed
go back to reference Risch N (1990a) Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. Am J Hum Genet 46(2):242–253PubMed Risch N (1990a) Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. Am J Hum Genet 46(2):242–253PubMed
go back to reference Risch N (1990b) Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am J Hum Genet 46(2):229–241PubMed Risch N (1990b) Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am J Hum Genet 46(2):229–241PubMed
go back to reference Risch N (1990c) Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 46(2):222–228PubMed Risch N (1990c) Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 46(2):222–228PubMed
go back to reference Risch N (1990) Genetic linkage and complex diseases, with special reference to psychiatric disorders. Genet Epidemiol 7(1):3–16 (discussion 7–45) Risch N (1990) Genetic linkage and complex diseases, with special reference to psychiatric disorders. Genet Epidemiol 7(1):3–16 (discussion 7–45)
go back to reference Risch N, Merikangas KR (1993) Linkage studies of psychiatric disorders. Eur Arch Psychiatry Clin Neurosci 243(3–4):143–149CrossRefPubMed Risch N, Merikangas KR (1993) Linkage studies of psychiatric disorders. Eur Arch Psychiatry Clin Neurosci 243(3–4):143–149CrossRefPubMed
go back to reference Risch N, Teng J (1998) The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases I. DNA pooling. Genome Res 8(12):1273–1288PubMed Risch N, Teng J (1998) The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases I. DNA pooling. Genome Res 8(12):1273–1288PubMed
go back to reference Risch N, Zhang H (1995) Extreme discordant sib pairs for mapping quantitative trait loci in humans. Science 268(5217):1584–1589CrossRefPubMed Risch N, Zhang H (1995) Extreme discordant sib pairs for mapping quantitative trait loci in humans. Science 268(5217):1584–1589CrossRefPubMed
go back to reference Schliekelman P, Slatkin M (2002) Multiplex relative risk and estimation of the number of loci underlying an inherited disease. Am J Hum Genet 71(6):1369–1385CrossRefPubMed Schliekelman P, Slatkin M (2002) Multiplex relative risk and estimation of the number of loci underlying an inherited disease. Am J Hum Genet 71(6):1369–1385CrossRefPubMed
go back to reference Service S, DeYoung J, Karayiorgou M, Roos JL, Pretorious H, Bedoya G et al (2006) Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies. Nat Genet 38(5):556–560CrossRefPubMed Service S, DeYoung J, Karayiorgou M, Roos JL, Pretorious H, Bedoya G et al (2006) Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies. Nat Genet 38(5):556–560CrossRefPubMed
go back to reference Sheehan K, Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M et al (2005) Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Mol Psychiatry 10(10):944–949CrossRefPubMed Sheehan K, Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M et al (2005) Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Mol Psychiatry 10(10):944–949CrossRefPubMed
go back to reference Slatkin M (2008) Genotype-specific recurrence risks as indicators of the genetic architecture of complex diseases. Am J Hum Genet 83(1):120–126CrossRefPubMed Slatkin M (2008) Genotype-specific recurrence risks as indicators of the genetic architecture of complex diseases. Am J Hum Genet 83(1):120–126CrossRefPubMed
go back to reference Slatkin M (2009) Epigenetic inheritance and the missing heritability problem. Genetics 182(3):845–850CrossRefPubMed Slatkin M (2009) Epigenetic inheritance and the missing heritability problem. Genetics 182(3):845–850CrossRefPubMed
go back to reference Smith AK, Mick E, Faraone SV (2009) Advances in genetic studies of attention-deficit/hyperactivity disorder. Curr Psychiatry Rep 11(2):143–148CrossRefPubMed Smith AK, Mick E, Faraone SV (2009) Advances in genetic studies of attention-deficit/hyperactivity disorder. Curr Psychiatry Rep 11(2):143–148CrossRefPubMed
go back to reference Spencer TJ, Biederman J, Mick E (2007) Attention-deficit/hyperactivity disorder: diagnosis, lifespan, comorbidities, and neurobiology. J Pediatr Psychol 32(6):631–642CrossRefPubMed Spencer TJ, Biederman J, Mick E (2007) Attention-deficit/hyperactivity disorder: diagnosis, lifespan, comorbidities, and neurobiology. J Pediatr Psychol 32(6):631–642CrossRefPubMed
go back to reference Stricker C, Fernando RL, Elston RC (1995) Linkage analysis with an alternative formulation for the mixed model of inheritance: the finite polygenic mixed model. Genetics 141(4):1651–1656PubMed Stricker C, Fernando RL, Elston RC (1995) Linkage analysis with an alternative formulation for the mixed model of inheritance: the finite polygenic mixed model. Genetics 141(4):1651–1656PubMed
go back to reference Sugita S, Ichtchenko K, Khvotchev M, Sudhof TC (1998) alpha-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors G-protein coupling not required for triggering exocytosis. J Biol Chem 273(49):32715–32724CrossRefPubMed Sugita S, Ichtchenko K, Khvotchev M, Sudhof TC (1998) alpha-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors G-protein coupling not required for triggering exocytosis. J Biol Chem 273(49):32715–32724CrossRefPubMed
go back to reference Thapar A, O’Donovan M, Owen MJ (2005) The genetics of attention deficit hyperactivity disorder. Hum Mol Genet 14 Spec No. 2:R275–R282 Thapar A, O’Donovan M, Owen MJ (2005) The genetics of attention deficit hyperactivity disorder. Hum Mol Genet 14 Spec No. 2:R275–R282
go back to reference van den Oord EJ, Boomsma DI, Verhulst FC (1994) A study of problem behaviors in 10- to 15-year-old biologically related and unrelated international adoptees. Behav Genet 24(3):193–205CrossRefPubMed van den Oord EJ, Boomsma DI, Verhulst FC (1994) A study of problem behaviors in 10- to 15-year-old biologically related and unrelated international adoptees. Behav Genet 24(3):193–205CrossRefPubMed
go back to reference Waldman ID, Gizer IR (2006) The genetics of attention deficit hyperactivity disorder. Clin Psychol Rev 26(4):396–432CrossRefPubMed Waldman ID, Gizer IR (2006) The genetics of attention deficit hyperactivity disorder. Clin Psychol Rev 26(4):396–432CrossRefPubMed
go back to reference Willcutt EG, Pennington BF, Chhabildas NA, Friedman MC, Alexander J (1999) Psychiatric comorbidity associated with DSM-IV ADHD in a nonreferred sample of twins. J Am Acad Child Adolesc Psychiatry 38(11):1355–1362CrossRefPubMed Willcutt EG, Pennington BF, Chhabildas NA, Friedman MC, Alexander J (1999) Psychiatric comorbidity associated with DSM-IV ADHD in a nonreferred sample of twins. J Am Acad Child Adolesc Psychiatry 38(11):1355–1362CrossRefPubMed
go back to reference Wong ML, Arcos-Burgos M, Licinio J (2008) Frontiers in psychiatric research. Psychiatr Times 25(7):1–8 Wong ML, Arcos-Burgos M, Licinio J (2008) Frontiers in psychiatric research. Psychiatr Times 25(7):1–8
Metadata
Title
Toward a better understanding of ADHD: LPHN3 gene variants and the susceptibility to develop ADHD
Authors
Mauricio Arcos-Burgos
Maximilian Muenke
Publication date
01-11-2010
Publisher
Springer Vienna
Published in
ADHD Attention Deficit and Hyperactivity Disorders / Issue 3/2010
Print ISSN: 1866-6116
Electronic ISSN: 1866-6647
DOI
https://doi.org/10.1007/s12402-010-0030-2

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