Advertisement

The Genetic Basis of Bipolar Disorder

  • Liping Hou
  • Francis J. McMahonEmail author
Chapter
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

The high heritability of bipolar disorder (BD) means that a full understanding of etiology must account for the strong influence of inherited genetic variation. An energetic search for specific genetic risk factors over the past 25 years has begun to bear fruit, but most of the genetic risk for BD remains unexplained. In this chapter, we will review the genetic epidemiology of BD, studies aimed at identifying genes that confer risk for the illness, functional genomic studies that seek to elucidate the pathophysiology of BD from the level of genes and gene networks, and pharmacogenomic studies that aim to identify genetic markers of treatment outcome. We conclude with a view to future directions that may ultimately lead to a more complete understanding of this common, severe mental illness and better approaches to diagnosis and treatment.

Keywords

GWAS CACNA1C ANK3 TRANK1 CNV 16p11 dup Mania Depression 

Notes

Disclosures

Supported by the NIMH Intramural Research Program. Dr. Hou received additional support from the Brain & Behavior Research Foundation.

References

  1. Akula N, Barb J, Jiang X, Wendland JR, Choi KH, Sen SK, Hou L, Chen DT, Laje G, Johnson K, Lipska BK, Kleinman JE, Corrada-Bravo H, Detera-Wadleigh S, Munson PJ, McMahon FJ (2014) RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder. Mol Psychiatry 19(11):1179–1185PubMedCrossRefGoogle Scholar
  2. Alda M (2003) Pharmacogenetic aspects of bipolar disorder. Pharmacogenomics 4(1):35–40PubMedCrossRefGoogle Scholar
  3. Anglin RE, Mazurek MF, Tarnopolsky MA, Rosebush PI (2012) The mitochondrial genome and psychiatric illness. Am J Med Genet B Neuropsychiatr Genet 159B(7):749–759PubMedCrossRefGoogle Scholar
  4. Badner JA, Gershon ES (2002) Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 7(4):405–411PubMedCrossRefGoogle Scholar
  5. Basile VS, Ozdemir V, Masellis M, Walker ML, Meltzer HY, Lieberman JA, Potkin SG, Alva G, Kalow W, Macciardi FM, Kennedy JL (2000) A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia. Mol Psychiatry 5(4):410–417PubMedCrossRefGoogle Scholar
  6. Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152(6):1298–1307PubMedPubMedCentralCrossRefGoogle Scholar
  7. Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nothen MM, Georgi A, Schumacher J, Schwarz M, Abou Jamra R, Hofels S, Propping P, Satagopan J, Detera-Wadleigh SD, Hardy J, McMahon FJ (2008) A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 13(2):197–207PubMedCrossRefGoogle Scholar
  8. Berrettini WH (2000) Are schizophrenic and bipolar disorders related? A review of family and molecular studies. Biol Psychiatry 48(6):531–538PubMedCrossRefGoogle Scholar
  9. Bertelsen A, Harvald B, Hauge M (1977) A Danish twin study of manic-depressive disorders. Br J Psychiatry 130:330–351PubMedCrossRefGoogle Scholar
  10. Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Human Genet 32(3):314–331Google Scholar
  11. Bremer T, Diamond C, McKinney R, Shehktman T, Barrett TB, Herold C, Kelsoe JR (2007) The pharmacogenetics of lithium response depends upon clinical co-morbidity. Mol Diagn Ther 11(3):161–170PubMedCrossRefGoogle Scholar
  12. Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, McCarthy S, Sebat J, Gage FH (2011) Modelling schizophrenia using human induced pluripotent stem cells. Nature 473(7346):221–225PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bryois J, Buil A, Evans DM, Kemp JP, Montgomery SB, Conrad DF, Ho KM, Ring S, Hurles M, Deloukas P, Davey Smith G, Dermitzakis ET (2014) Cis and trans effects of human genomic variants on gene expression. PLoS Genet 10(7), e1004461PubMedPubMedCentralCrossRefGoogle Scholar
  14. Calkin C, Alda M (2012) Beyond the guidelines for bipolar disorder: practical issues in long-term treatment with lithium. Can J Psychiatry 57(7):437–445PubMedGoogle Scholar
  15. Chen CH, Lee CS, Lee MT, Ouyang WC, Chen CC, Chong MY, Wu JY, Tan HK, Lee YC, Chuo LJ, Chiu NY, Tsang HY, Chang TJ, Lung FW, Chiu CH, Chang CH, Chen YS, Hou YM, Chen CC, Lai TJ, Tung CL, Chen CY, Lane HY, Su TP, Feng J, Lin JJ, Chang CJ, Teng PR, Liu CY, Chen CK, Liu IC, Chen JJ, Lu T, Fan CC, Wu CK, Li CF, Wang KH, Wu LS, Peng HL, Chang CP, Lu LS, Chen YT, Cheng AT, Taiwan Bipolar C (2014) Variant GADL1 and response to lithium therapy in bipolar I disorder. N Engl J Med 370(2):119–128PubMedCrossRefGoogle Scholar
  16. Chowdhury NI, Tiwari AK, Souza RP, Zai CC, Shaikh SA, Chen S, Liu F, Lieberman JA, Meltzer HY, Malhotra AK, Kennedy JL, Muller DJ (2013) Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene. Pharmacogenomics 13(3):272–279CrossRefGoogle Scholar
  17. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT (2004) Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428(6982):486PubMedCrossRefGoogle Scholar
  18. Collins AL, Sullivan PF (2013) Genome-wide association studies in psychiatry: what have we learned? Br J Psychiatry 202(1):1–4, http://commonmind.org/WP/. Accessed 15 Oct 2015PubMedPubMedCentralCrossRefGoogle Scholar
  19. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121):819–823PubMedPubMedCentralCrossRefGoogle Scholar
  20. Consortium EP (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414):57–74CrossRefGoogle Scholar
  21. Craddock N, Forty L (2006) Genetics of affective (mood) disorders. Eur J Human Genet 14(6):660–668CrossRefGoogle Scholar
  22. Cross-Disorder Group of the Psychiatric Genomics Consortium (2013a) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381(9875):1371–1379PubMedCentralCrossRefGoogle Scholar
  23. Cross-Disorder Group of the Psychiatric Genomics Consortium (2013b) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 45(9):984–994PubMedCentralCrossRefGoogle Scholar
  24. De Luca V, Muller DJ, Hwang R, Lieberman JA, Volavka J, Meltzer HY, Kennedy JL (2007) HTR2C haplotypes and antipsychotics-induced weight gain: X-linked multimarker analysis. Hum Psychopharmacol 22(7):463–467PubMedCrossRefGoogle Scholar
  25. Detera-Wadleigh SD, McMahon FJ (2006) G72/G30 in schizophrenia and bipolar disorder: review and meta-analysis. Biol Psychiatry 60(2):106–114PubMedCrossRefGoogle Scholar
  26. Dmitrzak-Weglarz M, Rybakowski JK, Suwalska A, Slopien A, Czerski PM, Leszczynska-Rodziewicz A, Hauser J (2005) Association studies of 5-HT2A and 5-HT2C serotonin receptor gene polymorphisms with prophylactic lithium response in bipolar patients. Pharmacol Rep 57(6):761–765PubMedGoogle Scholar
  27. Eaves LJ (1978) Twins as a basis for the causal analysis of human personality. Prog Clin Biol Res 24A:151–174PubMedGoogle Scholar
  28. Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman DE (1987) Bipolar affective disorders linked to DNA markers on chromosome 11. Nature 325(6107):783–787PubMedCrossRefGoogle Scholar
  29. Falconer DS (1981) Introduction to quantitative genetics. Longmans Green, LondonGoogle Scholar
  30. Farmer A, Elkin A, McGuffin P (2007) The genetics of bipolar affective disorder. Curr Opin Psychiatry 20(1):8–12PubMedCrossRefGoogle Scholar
  31. Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P, Georgieva L, Rees E, Palta P, Ruderfer DM, Carrera N, Humphreys I, Johnson JS, Roussos P, Barker DD, Banks E, Milanova V, Grant SG, Hannon E, Rose SA, Chambert K, Mahajan M, Scolnick EM, Moran JL, Kirov G, Palotie A, McCarroll SA, Holmans P, Sklar P, Owen MJ, Purcell SM, O’Donovan MC (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature 506(7487):179–184PubMedPubMedCentralCrossRefGoogle Scholar
  32. Gaedigk A, Leeder JS (2014) CYP2D6 and pharmacogenomics: where does future research need to focus? Part 1: Technical aspects. Pharmacogenomics 15(4):407–410PubMedCrossRefGoogle Scholar
  33. Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI Jr, Goldin LR, Bunney WE Jr (1982) A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands. Arch Gen Psychiatry 39(10):1157–1167PubMedCrossRefGoogle Scholar
  34. Goldberg AD, Allis CD, Bernstein E (2007) Epigenetics: a landscape takes shape. Cell 128(4):635–638PubMedCrossRefGoogle Scholar
  35. Goldstein JI, Jarskog LF, Hilliard C, Alfirevic A, Duncan L, Fourches D, Huang H, Lek M, Neale BM, Ripke S, Shianna K, Szatkiewicz JP, Tropsha A, van den Oord EJ, Cascorbi I, Dettling M, Gazit E, Goff DC, Holden AL, Kelly DL, Malhotra AK, Nielsen J, Pirmohamed M, Rujescu D, Werge T, Levy DL, Josiassen RC, Kennedy JL, Lieberman JA, Daly MJ, Sullivan PF (2014) Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. Nat Commun 5:4757PubMedPubMedCentralCrossRefGoogle Scholar
  36. Gratten J, Visscher PM, Mowry BJ, Wray NR (2013) Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease. Nat Genet 45(3):234–238PubMedCrossRefGoogle Scholar
  37. Green EK, Rees E, Walters JT, Smith KG, Forty L, Grozeva D, Moran JL, Sklar P, Ripke S, Chambert KD, Genovese G, McCarroll SA, Jones I, Jones L, Owen MJ, O’Donovan MC, Craddock N, Kirov G (2016) Copy number variation in bipolar disorder. Mol Psychiatry 21(1):89–93PubMedCrossRefGoogle Scholar
  38. Guha S, Rees E, Darvasi A, Ivanov D, Ikeda M, Bergen SE, Magnusson PK, Cormican P, Morris D, Gill M, Cichon S, Rosenfeld JA, Lee A, Gregersen PK, Kane JM, Malhotra AK, Rietschel M, Nothen MM, Degenhardt F, Priebe L, Breuer R, Strohmaier J, Ruderfer DM, Moran JL, Chambert KD, Sanders AR, Shi J, Kendler K, Riley B, O’Neill T, Walsh D, Malhotra D, Corvin A, Purcell S, Sklar P, Iwata N, Hultman CM, Sullivan PF, Sebat J, McCarthy S, Gejman PV, Levinson DF, Owen MJ, O’Donovan MC, Lencz T, Kirov G, Molecular Genetics of Schizophrenia C, Wellcome Trust Case Control C (2013) Implication of a rare deletion at distal 16p11.2 in schizophrenia. JAMA Psychiatry 70(3):253–260PubMedPubMedCentralCrossRefGoogle Scholar
  39. Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY et al (1983) A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 306(5940):234–238PubMedCrossRefGoogle Scholar
  40. Hayden EP, Nurnberger JI Jr (2006) Molecular genetics of bipolar disorder. Genes Brain Behav 5(1):85–95PubMedCrossRefGoogle Scholar
  41. Hernandez DG, Nalls MA, Moore M, Chong S, Dillman A, Trabzuni D, Gibbs JR, Ryten M, Arepalli S, Weale ME, Zonderman AB, Troncoso J, O’Brien R, Walker R, Smith C, Bandinelli S, Traynor BJ, Hardy J, Singleton AB, Cookson MR (2012) Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain. Neurobiol Dis 47(1):20–28PubMedPubMedCentralCrossRefGoogle Scholar
  42. Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, Rettie AE (2002) Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 287(13):1690–1698PubMedCrossRefGoogle Scholar
  43. Hou L, Heilbronner U, Degenhardt F, Adli M, Akiyama K, Akula N et al (2016) Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet 387(10023):1085–1093PubMedCrossRefGoogle Scholar
  44. Insel TR (2014) Brain somatic mutations: the dark matter of psychiatric genetics? Mol Psychiatry 19(2):156–158PubMedCrossRefGoogle Scholar
  45. International HapMap Consortium (2003) The International HapMap Project. Nature 426(6968):789–796CrossRefGoogle Scholar
  46. Ioannidis JP (2003) Genetic associations: false or true? Trends Mol Med 9(4):135–138PubMedCrossRefGoogle Scholar
  47. Ioannidis JP (2007) Non-replication and inconsistency in the genome-wide association setting. Hum Hered 64(4):203–213PubMedCrossRefGoogle Scholar
  48. Kato T (2007) Molecular genetics of bipolar disorder and depression. Psychiatry Clin Neurosci 61(1):3–19PubMedCrossRefGoogle Scholar
  49. Kelsoe JR, Ginns EI, Egeland JA, Gerhard DS, Goldstein AM, Bale SJ, Pauls DL, Long RT, Kidd KK, Conte G et al (1989) Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature 342(6247):238–243PubMedCrossRefGoogle Scholar
  50. Kieseppa T, Partonen T, Haukka J, Kaprio J, Lonnqvist J (2004) High concordance of bipolar I disorder in a nationwide sample of twins. Am J Psychiatry 161(10):1814–1821PubMedCrossRefGoogle Scholar
  51. Knowlton RG, Cohen-Haguenauer O, Van Cong N, Frezal J, Brown VA, Barker D, Braman JC, Schumm JW, Tsui LC, Buchwald M et al (1985) A polymorphic DNA marker linked to cystic fibrosis is located on chromosome 7. Nature 318(6044):380–382PubMedCrossRefGoogle Scholar
  52. Laje G, McMahon FJ (2007) The pharmacogenetics of major depression: past, present, and future. Biol Psychiatry 62(11):1205–1207PubMedCrossRefGoogle Scholar
  53. Lencz T, Robinson DG, Xu K, Ekholm J, Sevy S, Gunduz-Bruce H, Woerner MG, Kane JM, Goldman D, Malhotra AK (2006) DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am J Psychiatry 163(3):529–531PubMedCrossRefGoogle Scholar
  54. Lester BM, Tronick E, Nestler E, Abel T, Kosofsky B, Kuzawa CW, Marsit CJ, Maze I, Meaney MJ, Monteggia LM, Reul JM, Skuse DH, Sweatt JD, Wood MA (2011) Behavioral epigenetics. Ann NY Acad Sci 1226:14–33PubMedPubMedCentralCrossRefGoogle Scholar
  55. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM (2009) Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373(9659):234–239PubMedCrossRefGoogle Scholar
  56. Luxenburger H (1930) Psychiatrisch-neurologische Zwillings pathologie. Zbl Ges Neurol Psychiat 56:145–180Google Scholar
  57. Malhotra AK, Correll CU, Chowdhury NI, Muller DJ, Gregersen PK, Lee AT, Tiwari AK, Kane JM, Fleischhacker WW, Kahn RS, Ophoff RA, Meltzer HY, Lencz T, Kennedy JL (2012) Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain. Arch Gen Psychiatry 69(9):904–912PubMedPubMedCentralCrossRefGoogle Scholar
  58. Mathews CA, Reus VI (2001) Assortative mating in the affective disorders: a systematic review and meta-analysis. Compr Psychiatry 42(4):257–262PubMedCrossRefGoogle Scholar
  59. McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A (2003) The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 60(5):497–502PubMedCrossRefGoogle Scholar
  60. McInnis MG, McMahon FJ, Chase GA, Simpson SG, Ross CA, DePaulo JR Jr (1993) Anticipation in bipolar affective disorder. Am J Hum Genet 53(2):385–390PubMedPubMedCentralGoogle Scholar
  61. McMahon FJ, Stine OC, Meyers DA, Simpson SG, DePaulo JR (1995) Patterns of maternal transmission in bipolar affective disorder. Am J Hum Genet 56(6):1277–1286PubMedPubMedCentralGoogle Scholar
  62. McPherson JD, Marra M, Hillier L, Waterston RH, Chinwalla A, Wallis J, Sekhon M, Wylie K, Mardis ER, Wilson RK, Fulton R, Kucaba TA, Wagner-McPherson C, Barbazuk WB, Gregory SG, Humphray SJ, French L, Evans RS, Bethel G, Whittaker A, Holden JL, McCann OT, Dunham A, Soderlund C, Scott CE, Bentley DR, Schuler G, Chen HC, Jang W, Green ED, Idol JR, Maduro VV, Montgomery KT, Lee E, Miller A, Emerling S, Kucherlapati RS, Kucherlapati R, Scherer S, Gorrell JH, Sodergren E, Clerc-Blankenburg K, Tabor P, Naylor S, Garcia D, de Jong PJ, Catanese JJ, Nowak N, Osoegawa K, Qin S, Rowen L, Madan A, Dors M, Hood L, Trask B, Friedman C, Massa H, Cheung VG, Kirsch IR, Reid T, Yonescu R, Weissenbach J, Bruls T, Heilig R, Branscomb E, Olsen A, Doggett N, Cheng JF, Hawkins T, Myers RM, Shang J, Ramirez L, Schmutz J, Velasquez O, Dixon K, Stone NE, Cox DR, Haussler D, Kent WJ, Furey T, Rogic S, Kennedy S, Jones S, Rosenthal A, Wen G, Schilhabel M, Gloeckner G, Nyakatura G, Siebert R, Schlegelberger B, Korenberg J, Chen XN, Fujiyama A, Hattori M, Toyoda A, Yada T, Park HS, Sakaki Y, Shimizu N, Asakawa S, Kawasaki K, Sasaki T, Shintani A, Shimizu A, Shibuya K, Kudoh J, Minoshima S, Ramser J, Seranski P, Hoff C, Poustka A, Reinhardt R, Lehrach H, International Human Genome Mapping C (2001) A physical map of the human genome. Nature 409(6822):934–941PubMedCrossRefGoogle Scholar
  63. McQueen MB, Devlin B, Faraone SV, Nimgaonkar VL, Sklar P, Smoller JW, Abou Jamra R, Albus M, Bacanu SA, Baron M, Barrett TB, Berrettini W, Blacker D, Byerley W, Cichon S, Coryell W, Craddock N, Daly MJ, Depaulo JR, Edenberg HJ, Foroud T, Gill M, Gilliam TC, Hamshere M, Jones I, Jones L, Juo SH, Kelsoe JR, Lambert D, Lange C, Lerer B, Liu J, Maier W, Mackinnon JD, McInnis MG, McMahon FJ, Murphy DL, Nothen MM, Nurnberger JI, Pato CN, Pato MT, Potash JB, Propping P, Pulver AE, Rice JP, Rietschel M, Scheftner W, Schumacher J, Segurado R, Van Steen K, Xie W, Zandi PP, Laird NM (2005) Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q. Am J Hum Genet 77(4):582–595PubMedPubMedCentralCrossRefGoogle Scholar
  64. Mendlewicz J, Rainer JD (1977) Adoption study supporting genetic transmission in manic–depressive illness. Nature 268(5618):327–329PubMedCrossRefGoogle Scholar
  65. Morrow EM, Yoo SY, Flavell SW, Kim TK, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321(5886):218–223PubMedPubMedCentralCrossRefGoogle Scholar
  66. Moser G, Lee SH, Hayes BJ, Goddard ME, Wray NR, Visscher PM (2015) Simultaneous discovery, estimation and prediction analysis of complex traits using a bayesian mixture model. PLoS Genet 11(4), e1004969PubMedPubMedCentralCrossRefGoogle Scholar
  67. Opgen-Rhein C, Brandl EJ, Muller DJ, Neuhaus AH, Tiwari AK, Sander T, Dettling M (2010) Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics 11(6):773–780PubMedCrossRefGoogle Scholar
  68. Perlis RH, Smoller JW, Ferreira MA, McQuillin A, Bass N, Lawrence J, Sachs GS, Nimgaonkar V, Scolnick EM, Gurling H, Sklar P, Purcell S (2009) A genome wide association study of response to lithium for prevention of recurrence in bipolar disorder. Am J Psychiatry 166(6):718–725PubMedPubMedCentralCrossRefGoogle Scholar
  69. Pritchard JK (2001) Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 69(1):124–137PubMedPubMedCentralCrossRefGoogle Scholar
  70. Propping P (2005) The biography of psychiatric genetics: from early achievements to historical burden, from an anxious society to critical geneticists. Am J Med Genet B Neuropsychiatr Genet 136B(1):2–7PubMedCrossRefGoogle Scholar
  71. Reus VI, Freimer NB (1997) Understanding the genetic basis of mood disorders: where do we stand? Am J Hum Genet 60(6):1283–1288PubMedPubMedCentralCrossRefGoogle Scholar
  72. Rosanoff AJ, Handy LM, Plesset IR (1935) The etiology of manic-depressive syndromes with special reference to their occurrence in twins. Am J Psychiatry 91(4):725–762CrossRefGoogle Scholar
  73. Rybakowski JK, Suwalska A, Czerski PM, Dmitrzak-Weglarz M, Leszczynska-Rodziewicz A, Hauser J (2005) Prophylactic effect of lithium in bipolar affective illness may be related to serotonin transporter genotype. Pharmacol Rep 57(1):124–127PubMedGoogle Scholar
  74. Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, Moreno-De-Luca D, Chu SH, Moreau MP, Gupta AR, Thomson SA, Mason CE, Bilguvar K, Celestino-Soper PB, Choi M, Crawford EL, Davis L, Wright NR, Dhodapkar RM, DiCola M, DiLullo NM, Fernandez TV, Fielding-Singh V, Fishman DO, Frahm S, Garagaloyan R, Goh GS, Kammela S, Klei L, Lowe JK, Lund SC, McGrew AD, Meyer KA, Moffat WJ, Murdoch JD, O’Roak BJ, Ober GT, Pottenger RS, Raubeson MJ, Song Y, Wang Q, Yaspan BL, Yu TW, Yurkiewicz IR, Beaudet AL, Cantor RM, Curland M, Grice DE, Gunel M, Lifton RP, Mane SM, Martin DM, Shaw CA, Sheldon M, Tischfield JA, Walsh CA, Morrow EM, Ledbetter DH, Fombonne E, Lord C, Martin CL, Brooks AI, Sutcliffe JS, Cook EH Jr, Geschwind D, Roeder K, Devlin B, State MW (2011) Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70(5):863–885PubMedPubMedCentralCrossRefGoogle Scholar
  75. Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, Teran NA, Song Y, El-Fishawy P, Murtha RC, Choi M, Overton JD, Bjornson RD, Carriero NJ, Meyer KA, Bilguvar K, Mane SM, Sestan N, Lifton RP, Gunel M, Roeder K, Geschwind DH, Devlin B, State MW (2012) De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485(7397):237–241PubMedPubMedCentralCrossRefGoogle Scholar
  76. Schillevoort I, de Boer A, van der Weide J, Steijns LS, Roos RA, Jansen PA, Leufkens HG (2002) Antipsychotic-induced extrapyramidal syndromes and cytochrome P450 2D6 genotype: a case-control study. Pharmacogenetics 12(3):235–240PubMedCrossRefGoogle Scholar
  77. Schulze TG, Fangerau H, Propping P (2004) From degeneration to genetic susceptibility, from eugenics to genetics, from Bezugsziffer to LOD score: the history of psychiatric genetics. Int Rev Psychiatry 16(4):246–259PubMedCrossRefGoogle Scholar
  78. Schulze TG, Alda M, Adli M, Akula N, Ardau R, Bui ET, Chillotti C, Cichon S, Czerski P, Del Zompo M, Detera-Wadleigh SD, Grof P, Gruber O, Hashimoto R, Hauser J, Hoban R, Iwata N, Kassem L, Kato T, Kittel-Schneider S, Kliwicki S, Kelsoe JR, Kusumi I, Laje G, Leckband SG, Manchia M, Macqueen G, Masui T, Ozaki N, Perlis RH, Pfennig A, Piccardi P, Richardson S, Rouleau G, Reif A, Rybakowski JK, Sasse J, Schumacher J, Severino G, Smoller JW, Squassina A, Turecki G, Young LT, Yoshikawa T, Bauer M, McMahon FJ (2010) The International Consortium on Lithium Genetics (ConLiGen): an initiative by the NIMH and IGSLI to study the genetic basis of response to lithium treatment. Neuropsychobiology 62(1):72–78PubMedPubMedCentralCrossRefGoogle Scholar
  79. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimaki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M (2007) Strong association of de novo copy number mutations with autism. Science 316(5823):445–449PubMedPubMedCentralCrossRefGoogle Scholar
  80. Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger JI Jr, Craddock N, DePaulo JR, Baron M, Gershon ES, Ekholm J, Cichon S, Turecki G, Claes S, Kelsoe JR, Schofield PR, Badenhop RF, Morissette J, Coon H, Blackwood D, McInnes LA, Foroud T, Edenberg HJ, Reich T, Rice JP, Goate A, McInnis MG, McMahon FJ, Badner JA, Goldin LR, Bennett P, Willour VL, Zandi PP, Liu J, Gilliam C, Juo SH, Berrettini WH, Yoshikawa T, Peltonen L, Lonnqvist J, Nothen MM, Schumacher J, Windemuth C, Rietschel M, Propping P, Maier W, Alda M, Grof P, Rouleau GA, Del-Favero J, Van Broeckhoven C, Mendlewicz J, Adolfsson R, Spence MA, Luebbert H, Adams LJ, Donald JA, Mitchell PB, Barden N, Shink E, Byerley W, Muir W, Visscher PM, Macgregor S, Gurling H, Kalsi G, McQuillin A, Escamilla MA, Reus VI, Leon P, Freimer NB, Ewald H, Kruse TA, Mors O, Radhakrishna U, Blouin JL, Antonarakis SE, Akarsu N (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, Part III: Bipolar disorder. Am J Hum Genet 73(1):49–62PubMedPubMedCentralCrossRefGoogle Scholar
  81. Seifuddin F, Pirooznia M, Judy JT, Goes FS, Potash JB, Zandi PP (2013) Systematic review of genome-wide gene expression studies of bipolar disorder. BMC Psychiatry 13(1):213PubMedPubMedCentralCrossRefGoogle Scholar
  82. Shuldiner AR, O’Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA (2009) Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302(8):849–857PubMedPubMedCentralCrossRefGoogle Scholar
  83. Sklar P, Smoller JW, Fan J, Ferreira MA, Perlis RH, Chambert K, Nimgaonkar VL, McQueen MB, Faraone SV, Kirby A, de Bakker PI, Ogdie MN, Thase ME, Sachs GS, Todd-Brown K, Gabriel SB, Sougnez C, Gates C, Blumenstiel B, Defelice M, Ardlie KG, Franklin J, Muir WJ, McGhee KA, MacIntyre DJ, McLean A, VanBeck M, McQuillin A, Bass NJ, Robinson M, Lawrence J, Anjorin A, Curtis D, Scolnick EM, Daly MJ, Blackwood DH, Gurling HM, Purcell SM (2008) Whole-genome association study of bipolar disorder. Mol Psychiatry 13(6):558–569PubMedPubMedCentralCrossRefGoogle Scholar
  84. Song J, Bergen SE, Kuja-Halkola R, Larsson H, Landen M, Lichtenstein P (2015) Bipolar disorder and its relation to major psychiatric disorders: a family-based study in the Swedish population. Bipolar Disord 17(2):184–193PubMedCrossRefGoogle Scholar
  85. Stine OC, Xu J, Koskela R, McMahon FJ, Gschwend M, Friddle C, Clark CD, McInnis MG, Simpson SG, Breschel TS, Vishio E, Riskin K, Feilotter H, Chen E, Shen S, Folstein S, Meyers DA, Botstein D, Marr TG, DePaulo JR (1995) Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect. Am J Hum Genet 57(6):1384–1394PubMedPubMedCentralGoogle Scholar
  86. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676PubMedCrossRefGoogle Scholar
  87. Tanaka E, Hisawa S (1999) Clinically significant pharmacokinetic drug interactions with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450 system. J Clin Pharm Ther 24(1):7–16PubMedCrossRefGoogle Scholar
  88. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (2001) The sequence of the human genome. Science 291(5507):1304–1351PubMedCrossRefGoogle Scholar
  89. Verhoeven JE, Revesz D, Epel ES, Lin J, Wolkowitz OM, Penninx BW (2014) Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study. Mol Psychiatry 19(8):895–901PubMedCrossRefGoogle Scholar
  90. Visscher PM, Hill WG, Wray NR (2008) Heritability in the genomics era–concepts and misconceptions. Nat Rev Genet 9(4):255–266PubMedCrossRefGoogle Scholar
  91. Wainwright BJ, Scambler PJ, Schmidtke J, Watson EA, Law HY, Farrall M, Cooke HJ, Eiberg H, Williamson R (1985) Localization of cystic fibrosis locus to human chromosome 7cen-q22. Nature 318(6044):384–385PubMedCrossRefGoogle Scholar
  92. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, Kusenda M, Malhotra D, Bhandari A, Stray SM, Rippey CF, Roccanova P, Makarov V, Lakshmi B, Findling RL, Sikich L, Stromberg T, Merriman B, Gogtay N, Butler P, Eckstrand K, Noory L, Gochman P, Long R, Chen Z, Davis S, Baker C, Eichler EE, Meltzer PS, Nelson SF, Singleton AB, Lee MK, Rapoport JL, King MC, Sebat J (2008) Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320(5875):539–543PubMedCrossRefGoogle Scholar
  93. Weissman MM, Gershon ES, Kidd KK, Prusoff BA, Leckman JF, Dibble E, Hamovit J, Thompson WD, Pauls DL, Guroff JJ (1984) Psychiatric disorders in the relatives of probands with affective disorders. The Yale University–National Institute of Mental Health Collaborative Study. Arch Gen Psychiatry 41(1):13–21PubMedCrossRefGoogle Scholar
  94. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678CrossRefGoogle Scholar
  95. Wender PH, Kety SS, Rosenthal D, Schulsinger F, Ortmann J, Lunde I (1986) Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Arch Gen Psychiatry 43(10):923–929PubMedCrossRefGoogle Scholar
  96. Winokur G (1975) The Iowa 500: heterogeneity and course in manic-depressive illness (bipolar). Compr Psychiatry 16(2):125–131PubMedCrossRefGoogle Scholar
  97. Wray NR, Lee SH, Mehta D, Vinkhuyzen AA, Dudbridge F, Middeldorp CM (2014) Research review: polygenic methods and their application to psychiatric traits. J Child Psychol Psychiatry 55(10):1068–1087PubMedCrossRefGoogle Scholar
  98. Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M (2008) Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet 40(7):880–885PubMedCrossRefGoogle Scholar
  99. Xu B, Roos JL, Dexheimer P, Boone B, Plummer B, Levy S, Gogos JA, Karayiorgou M (2011) Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nat Genet 43(9):864–868PubMedPubMedCentralCrossRefGoogle Scholar
  100. Xu B, Ionita-Laza I, Roos JL, Boone B, Woodrick S, Sun Y, Levy S, Gogos JA, Karayiorgou M (2012) De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat Genet 44(12):1365–1369PubMedPubMedCentralCrossRefGoogle Scholar
  101. Yamanouchi Y, Iwata N, Suzuki T, Kitajima T, Ikeda M, Ozaki N (2003) Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone. Pharmacogenomics 3(6):356–361CrossRefGoogle Scholar
  102. Yunis JJ, Corzo D, Salazar M, Lieberman JA, Howard A, Yunis EJ (1995) HLA associations in clozapine-induced agranulocytosis. Blood 86(3):1177–1183PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland (outside the USA)  2016

Authors and Affiliations

  1. 1.Human Genetics Branch, Intramural Research ProgramNational Institutes of HealthBethesdaUSA
  2. 2.Human Genetics BranchNational Institutes of HealthBethesdaUSA

Personalised recommendations