Data from the Genetic Association Information Network (GAIN) genome-wide association study (GWAS) in major depressive disorder (MDD) were used to explore previously reported candidate gene and single-nucleotide polymorphism (SNP) associations in MDD. A systematic literature search of candidate genes associated with MDD in case–control studies was performed before the results of the GAIN MDD study became available. Measured and imputed candidate SNPs and genes were tested in the GAIN MDD study encompassing 1738 cases and 1802 controls. Imputation was used to increase the number of SNPs from the GWAS and to improve coverage of SNPs in the candidate genes selected. Tests were carried out for individual SNPs and the entire gene using different statistical approaches, with permutation analysis as the final arbiter. In all, 78 papers reporting on 57 genes were identified, from which 92 SNPs could be mapped. In the GAIN MDD study, two SNPs were associated with MDD: C5orf20 (rs12520799; P=0.038; odds ratio (OR) AT=1.10, 95% CI 0.95–1.29; OR TT=1.21, 95% confidence interval (CI) 1.01–1.47) and NPY (rs16139; P=0.034; OR C allele=0.73, 95% CI 0.55–0.97), constituting a direct replication of previously identified SNPs. At the gene level, TNF (rs76917; OR T=1.35, 95% CI 1.13–1.63; P=0.0034) was identified as the only gene for which the association with MDD remained significant after correction for multiple testing. For SLC6A2 (norepinephrine transporter (NET)) significantly more SNPs (19 out of 100; P=0.039) than expected were associated while accounting for the linkage disequilibrium (LD) structure. Thus, we found support for involvement in MDD for only four genes. However, given the number of candidate SNPs and genes that were tested, even these significant may well be false positives. The poor replication may point to publication bias and false-positive findings in previous candidate gene studies, and may also be related to heterogeneity of the MDD phenotype as well as contextual genetic or environmental factors.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Manolio TA, Rodriguez LL, Brooks L, Abecasis G, Ballinger D, Daly M et al. New models of collaboration in genome-wide association studies: the Genetic Association Information Network. Nat Genet 2007; 39: 1045–1051.
Boomsma DI, Willemsen G, Sullivan PF, Heutink P, Meijer P, Sondervan D et al. Genome-wide association of major depression: description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects. Eur J Hum Genet 2008; 16: 335–342.
The Wellcome Trust Case-Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447: 661–678.
Sullivan PF, de Geus EJ, Willemsen G, James MR, Smit JH, Zandbelt T et al. Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Mol Psychiatry 2009; 14: 359–375.
Arking DE, Pfeufer A, Post W, Kao WH, Newton-Cheh C, Ikeda M et al. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet 2006; 38: 644–651.
Roeder K, Bacanu SA, Wasserman L, Devlin B . Using linkage genome scans to improve power of association in genome scans. Am J Hum Genet 2006; 78: 243–252.
Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K . A comprehensive review of genetic association studies. Genet Med 2002; 4: 45–61.
Munafo MR . Candidate gene studies in the 21st century: meta-analysis, mediation, moderation. Genes Brain Behav 2006; 5(Suppl 1): 3–8.
Lopez-Leon S, Janssens AC, Gonzalez-Zuloeta Ladd AM, Del-Favero J, Claes SJ, Oostra BA et al. Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry 2008; 13: 772–785.
Penninx BW, Beekman AT, Smit JH, Zitman FG, Nolen W, Spinhoven P et al. The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods. Int J Methods Psychiatr Res 2008; 17: 121–140.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association: Washington, DC, 1994.
World Health Organization. Composite International Diagnostic Interview (CIDI), Version 2.1.. World Health Organization: Geneva, Switzerland, 1997.
Marchini J, Howie B, Myers S, McVean G, Donnelly P . A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 2007; 39: 906–913.
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: 559–575.
Maes M, Delanghe J, Scharpe S, Meltzer HY, Cosyns P, Suy E et al. Haptoglobin phenotypes and gene frequencies in unipolar major depression. Am J Psychiatry 1994; 151: 112–116.
Koks S, Nikopensius T, Koido K, Maron E, Altmae S, Heinaste E et al. Analysis of SNP profiles in patients with major depressive disorder. Int J Neuropsychopharmacol 2006; 9: 167–174.
Zhang X, Gainetdinov RR, Beaulieu JM, Sotnikova TD, Burch LH, Williams RB et al. Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron 2005; 45: 11–16.
Blakely RD . Overview: a rare opportunity or just one less reason to be depressed. Neuron 2005; 48: 701–702; author reply 705–706.
Baghai TC, Binder EB, Schule C, Salyakina D, Eser D, Lucae S et al. Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism. Mol Psychiatry 2006; 11: 1003–1015.
Arking DE, Khera A, Xing C, Kao WH, Post W, Boerwinkle E et al. Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. PLoS ONE 2009; 4: e4333.
Muglia P, Tozzi F, Galwey NW, Francks C, Upmanyu R, Kong XQ et al. Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts. Mol Psychiatry; advance online publication, 23 December 2008; doi:10.1038/mp.2008.131.
Lucae S, Salyakina D, Barden N, Harvey M, Gagne B, Labbe M et al. P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Hum Mol Genet 2006; 15: 2438–2445.
Willis-Owen SA, Shifman S, Copley RR, Flint J . DCNP1: a novel candidate gene for major depression. Mol Psychiatry 2006; 11: 121–122.
Heilig M, Zachrisson O, Thorsell A, Ehnvall A, Mottagui-Tabar S, Sjogren M et al. Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. J Psychiatr Res 2004; 38: 113–121.
Inoue K, Itoh K, Yoshida K, Shimizu T, Suzuki T . Positive association between T-182C polymorphism in the norepinephrine transporter gene and susceptibility to major depressive disorder in a Japanese population. Neuropsychobiology 2004; 50: 301–304.
Jun TY, Pae CU, Hoon H, Chae JH, Bahk WM, Kim KS et al. Possible association between -G308A tumour necrosis factor-alpha gene polymorphism and major depressive disorder in the Korean population. Psychiatr Genet 2003; 13: 179–181.
Hek K, Mulder CL, Luijendijk HJ, van Duijn CM, Hofman A, Uitterlinden AG et al. The PCLO gene and depressive disorders: replication in a population-based study. Hum Mol Genet 2009; 19: 731–734.
Martinez FD . Gene-environment interactions in asthma: with apologies to William of Ockham. Proc Am Thorac Soc 2007; 4: 26–31.
Psychiatric GWAS Consortium Steering Committee. A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry 2009; 14: 10–17.
Frisch A, Postilnick D, Rockah R, Michaelovsky E, Postilnick S, Birman E et al. Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways. Mol Psychiatry 1999; 4: 389–392.
Manki H, Kanba S, Muramatsu T, Higuchi S, Suzuki E, Matsushita S et al. Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders. J Affect Disord 1996; 40: 7–13.
Su S, Zhao J, Bremner JD, Miller AH, Tang W, Bouzyk M et al. Serotonin transporter gene, depressive symptoms and interleukin-6. Circ Cardiovasc Genet 2009; 2: 614–620.
Wray NR, James MR, Gordon SD, Dumenil T, Ryan L, Coventry WL et al. Accurate, large-scale genotyping of 5HTTLPR and flanking single nucleotide polymorphisms in an association study of depression, anxiety, and personality measures. Biol Psychiatry 2009; 66: 468–476.
Arinami T, Yamada N, Yamakawa-Kobayashi K, Hamaguchi H, Toru M . Methylenetetrahydrofolate reductase variant and schizophrenia/depression. Am J Med Genet 1997; 74: 526–528.
Kelly CB, McDonnell AP, Johnston TG, Mulholland C, Cooper SJ, McMaster D et al. The MTHFR C677 T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol 2004; 18: 567–571.
Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD et al. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 2003; 23: 8788–8799.
Choi MJ, Kang RH, Ham BJ, Jeong HY, Lee MS . Serotonin receptor 2A gene polymorphism (-1438A/G) and short-term treatment response to citalopram. Neuropsychobiology 2005; 52: 155–162.
Choi MJ, Lee HJ, Lee HJ, Ham BJ, Cha JH, Ryu SH et al. Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene. Neuropsychobiology 2004; 49: 38–41.
Du L, Bakish D, Lapierre YD, Ravindran AV, Hrdina PD . Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am J Med Genet 2000; 96: 56–60.
Lerer B, Macciardi F, Segman RH, Adolfsson R, Blackwood D, Blairy S et al. Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder. Mol Psychiatry 2001; 6: 579–585.
Yamada K, Hattori E, Iwayama Y, Ohnishi T, Ohba H, Toyota T et al. Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression. Biol Psychiatry 2006; 60: 192–201.
Mendlewicz J, Oswald P, Claes S, Massat I, Souery D, Van Broeckhoven C et al. Patient-control association study of substance P-related genes in unipolar and bipolar affective disorders. Int J Neuropsychopharmacol 2005; 8: 505–513.
Covault J, Pettinati H, Moak D, Mueller T, Kranzler HR . Association of a long-chain fatty acid-CoA ligase 4 gene polymorphism with depression and with enhanced niacin-induced dermal erythema. Am J Med Genet B Neuropsychiatr Genet 2004; 127B: 42–47.
Su QR, Su LY, Su HR, Chen Q, Ren GY, Yin Y et al. Polymorphisms of androgen receptor gene in childhood and adolescent males with first-onset major depressive disorder and association with related symptomatology. Int J Neurosci 2007; 117: 903–917.
Saab YB, Gard PR, Yeoman MS, Mfarrej B, El-Moalem H, Ingram MJ . Renin-angiotensin-system gene polymorphisms and depression. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31: 1113–1118.
Holmes C, Russ C, Kirov G, Aitchison KJ, Powell JF, Collier DA et al. Apolipoprotein E: depressive illness, depressive symptoms, and Alzheimer's disease. Biol Psychiatry 1998; 43: 159–164.
Fan PL, Chen CD, Kao WT, Shu BC, Lung FW . Protective effect of the apo epsilon2 allele in major depressive disorder in Taiwanese. Acta Psychiatr Scand 2006; 113: 48–53.
van West D, Del-Favero J, Aulchenko Y, Oswald P, Souery D, Forsgren T et al. A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression. Mol Psychiatry 2004; 9: 287–292.
Hwang JP, Tsai SJ, Hong CJ, Yang CH, Lirng JF, Yang YM . The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression. Neurobiol Aging 2006; 27: 1834–1837.
Ribeiro L, Busnello JV, Cantor RM, Whelan F, Whittaker P, Deloukas P et al. The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. NeuroReport 2007; 18: 1291–1293.
Schumacher J, Jamra RA, Becker T, Ohlraun S, Klopp N, Binder EB et al. Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. Biol Psychiatry 2005; 58: 307–314.
Hashimoto R, Okada T, Kato T, Kosuga A, Tatsumi M, Kamijima K et al. The breakpoint cluster region gene on chromosome 22q11 is associated with bipolar disorder. Biol Psychiatry 2005; 57: 1097–1102.
Massat I, Souery D, Del-Favero J, Nothen M, Blackwood D, Muir W et al. Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. Mol Psychiatry 2005; 10: 598–605.
Funke B, Malhotra AK, Finn CT, Plocik AM, Lake SL, Lencz T et al. COMT genetic variation confers risk for psychotic and affective disorders: a case control study. Behav Brain Funct 2005; 1: 19.
Pae CU, Yu HS, Kim TS, Lee CU, Lee SJ, Jun TY et al. Monocyte chemoattractant protein-1 (MCP1) promoter -2518 polymorphism may confer a susceptibility to major depressive disorder in the Korean population. Psychiatry Res 2004; 127: 279–281.
Comings DE, Wu S, Rostamkhani M, McGue M, Iacono WG, MacMurray JP . Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women. Am J Med Genet 2002; 114: 527–529.
Lai IC, Hong CJ, Tsai SJ . Association study of nicotinic-receptor variants and major depressive disorder. J Affect Disord 2001; 66: 79–82.
Claes S, Villafuerte S, Forsgren T, Sluijs S, Del-Favero J, Adolfsson R et al. The corticotropin-releasing hormone binding protein is associated with major depression in a population from Northern Sweden. Biol Psychiatry 2003; 54: 867–872.
Liu Z, Zhu F, Wang G, Xiao Z, Wang H, Tang J et al. Association of corticotropin-releasing hormone receptor1 gene SNP and haplotype with major depression. Neurosci Lett 2006; 404: 358–362.
Villafuerte SM, Del-Favero J, Adolfsson R, Souery D, Massat I, Mendlewicz J et al. Gene-based SNP genetic association study of the corticotropin-releasing hormone receptor-2 (CRHR2) in major depression. Am J Med Genet 2002; 114: 222–226.
Dorado P, Penas-Lledo EM, Gonzalez AP, Caceres MC, Cobaleda J, Llerena A . Increased risk for major depression associated with the short allele of the serotonin transporter promoter region (5-HTTLPR-S) and the CYP2C9*3 allele. Fundam Clin Pharmacol 2007; 21: 451–453.
LLerena A, Berecz R, Dorado P, Gonzalez AP, Penas LEM, De La Rubia A . CYP2C9 gene and susceptibility to major depressive disorder. Pharmacogenomics J 2003; 3: 300–302.
Hashimoto R, Numakawa T, Ohnishi T, Kumamaru E, Yagasaki Y, Ishimoto T et al. Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. Hum Mol Genet 2006; 15: 3024–3033.
Dikeos DG, Papadimitriou GN, Avramopoulos D, Karadima G, Daskalopoulou EG, Souery D et al. Association between the dopamine D3 receptor gene locus (DRD3) and unipolar affective disorder. Psychiatr Genet 1999; 9: 189–195.
Serretti A, Lilli R, Di Bella D, Bertelli S, Nobile M, Novelli E et al. Dopamine receptor D4 gene is not associated with major psychoses. Am J Med Genet 1999; 88: 486–491.
Tsai SJ, Wang YC, Hong CJ, Chiu HJ . Association study of oestrogen receptor alpha gene polymorphism and suicidal behaviours in major depressive disorder. Psychiatr Genet 2003; 13: 19–22.
Geng YG, Su QR, Su LY, Chen Q, Ren GY, Shen SQ et al. Comparison of the polymorphisms of androgen receptor gene and estrogen alpha and beta gene between adolescent females with first-onset major depressive disorder and controls. Int J Neurosci 2007; 117: 539–547.
Thomson PA, Wray NR, Thomson AM, Dunbar DR, Grassie MA, Condie A et al. Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor. Mol Psychiatry 2005; 10: 470–478.
Henkel V, Baghai TC, Eser D, Zill P, Mergl R, Zwanzger P et al. The gamma amino butyric acid (GABA) receptor alpha-3 subunit gene polymorphism in unipolar depressive disorder: a genetic association study. Am J Med Genet B Neuropsychiatr Genet 2004; 126B: 82–87.
Tadokoro K, Hashimoto R, Tatsumi M, Kosuga A, Kamijima K, Kunugi H . The Gem interacting protein (GMIP) gene is associated with major depressive disorder. Neurogenetics 2005; 6: 127–133.
Cao MQ, Hu SY, Zhang CH, Xia DS . Study on the interrelationship between 5-HTTLPR/G-protein beta3 subunit (C825 T) polymorphisms and depressive disorder. Psychiatr Genet 2007; 17: 233–238.
Lee HJ, Cha JH, Ham BJ, Han CS, Kim YK, Lee SH et al. Association between a G-protein beta 3 subunit gene polymorphism and the symptomatology and treatment responses of major depressive disorders. Pharmacogenomics J 2004; 4: 29–33.
Zill P, Baghai TC, Zwanzger P, Schule C, Minov C, Riedel M et al. Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment. NeuroReport 2000; 11: 1893–1897.
Pae CU, Yu HS, Kim JJ, Lee CU, Lee SJ, Lee KU et al. BanI polymorphism of the cytosolic phospholipase A2 gene and mood disorders in the Korean population. Neuropsychobiology 2004; 49: 185–188.
Kolsch H, Ptok U, Majores M, Schmitz S, Rao ML, Maier W et al. Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer's disease. Psychiatr Genet 2004; 14: 97–100.
Schulze TG, Muller DJ, Krauss H, Scherk H, Ohlraun S, Syagailo YV et al. Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder. Am J Med Genet 2000; 96: 801–803.
Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW . Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response. Neuropsychopharmacology 2005; 30: 1719–1723.
Du L, Bakish D, Ravindran A, Hrdina PD . MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males. NeuroReport 2004; 15: 2097–2101.
Kunugi H, Hashimoto R, Yoshida M, Tatsumi M, Kamijima K . A missense polymorphism (S205 L) of the low-affinity neurotrophin receptor p75NTR gene is associated with depressive disorder and attempted suicide. Am J Med Genet B Neuropsychiatr Genet 2004; 129B: 44–46.
van Rossum EF, Binder EB, Majer M, Koper JW, Ising M, Modell S et al. Polymorphisms of the glucocorticoid receptor gene and major depression. Biol Psychiatry 2006; 59: 681–688.
van West D, Van Den Eede F, Del-Favero J, Souery D, Norrback KF, Van Duijn C et al. Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression. Neuropsychopharmacology 2006; 31: 620–627.
Wong ML, Whelan F, Deloukas P, Whittaker P, Delgado M, Cantor RM et al. Phosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response. Proc Natl Acad Sci USA 2006; 103: 15124–15129.
Ryu SH, Lee SH, Lee HJ, Cha JH, Ham BJ, Han CS et al. Association between norepinephrine transporter gene polymorphism and major depression. Neuropsychobiology 2004; 49: 174–177.
Nobile M, Cataldo MG, Giorda R, Battaglia M, Baschirotto C, Bellina M et al. A case-control and family-based association study of the 5-HTTLPR in pediatric-onset depressive disorders. Biol Psychiatry 2004; 56: 292–295.
Hoefgen B, Schulze TG, Ohlraun S, von Widdern O, Hofels S, Gross M et al. The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder. Biol Psychiatry 2005; 57: 247–251.
Cervilla JA, Rivera M, Molina E, Torres-Gonzalez F, Bellon JA, Moreno B et al. The 5-HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: the PREDICT-gene study. Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 912–917.
Grunblatt E, Loffler C, Zehetmayer S, Jungwirth S, Tragl KH, Riederer P et al. Association study of the 5-HTTLPR polymorphism and depression in 75-year-old nondemented subjects from the Vienna Transdanube Aging (VITA) study. J Clin Psychiatry 2006; 67: 1373–1378.
Munafo MR, Clark TG, Roberts KH, Johnstone EC . Neuroticism mediates the association of the serotonin transporter gene with lifetime major depression. Neuropsychobiology 2006; 53: 1–8.
Mann JJ, Huang YY, Underwood MD, Kassir SA, Oppenheim S, Kelly TM et al. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry 2000; 57: 729–738.
Ogilvie AD, Battersby S, Bubb VJ, Fink G, Harmar AJ, Goodwim GM et al. Polymorphism in serotonin transporter gene associated with susceptibility to major depression. Lancet 1996; 347: 731–733.
Liu W, Gu N, Feng G, Li S, Bai S, Zhang J et al. Tentative association of the serotonin transporter with schizophrenia and unipolar depression but not with bipolar disorder in Han Chinese. Pharmacogenetics 1999; 9: 491–495.
Domotor E, Sarosi A, Balogh G, Szekely A, Hejjas K, Sasvari-Szekely M et al. Association of neurocognitive endophenotype and STin2 polymorphism in major depressive disorder]. Neuropsychopharmacol Hung 2007; 9: 53–62.
Bozina N, Mihaljevic-Peles A, Sagud M, Jakovljevic M, Sertic J . Serotonin transporter polymorphism in Croatian patients with major depressive disorder. Psychiatr Danub 2006; 18: 83–89.
Battersby S, Ogilvie AD, Smith CA, Blackwood DH, Muir WJ, Quinn JP et al. Structure of a variable number tandem repeat of the serotonin transporter gene and association with affective disorder. Psychiatr Genet 1996; 6: 177–181.
Gutierrez B, Pintor L, Gasto C, Rosa A, Bertranpetit J, Vieta E et al. Variability in the serotonin transporter gene and increased risk for major depression with melancholia. Hum Genet 1998; 103: 319–322.
Schahab S, Heun R, Schmitz S, Maier W, Kolsch H . Association of polymorphism in the transcription factor LBP-1c/CP2/LSF gene with Alzheimer's disease and major depression. Dement Geriatr Cogn Disord 2006; 22: 95–98.
Tan EC, Chan AO, Tan CH, Mahendran R, Wang A, Chua HC . Case-control and linkage disequilibrium studies of the tryptophan hydroxylase gene polymorphisms and major depressive disorder. Psychiatr Genet 2003; 13: 151–154.
Gizatullin R, Zaboli G, Jonsson EG, Asberg M, Leopardi R . Haplotype analysis reveals tryptophan hydroxylase (TPH) 1 gene variants associated with major depression. Biol Psychiatry 2006; 59: 295–300.
Zill P, Baghai TC, Zwanzger P, Schule C, Eser D, Rupprecht R et al. SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression. Mol Psychiatry 2004; 9: 1030–1036.
Zhou Z, Roy A, Lipsky R, Kuchipudi K, Zhu G, Taubman J et al. Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations. Arch Gen Psychiatry 2005; 62: 1109–1118.
Koido K, Koks S, Nikopensius T, Maron E, Altmae S, Heinaste E et al. Polymorphisms in wolframin (WFS1) gene are possibly related to increased risk for mood disorders. Int J Neuropsychopharmacol 2005; 8: 235–244.
We thank Ting Wu for making the flow diagram in Figure 1.
The authors declare no conflict of interest.
About this article
Cite this article
Bosker, F., Hartman, C., Nolte, I. et al. Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry 16, 516–532 (2011). https://doi.org/10.1038/mp.2010.38
- candidate genes
- genome-wide association study
- major depressive disorder
- single-nucleotide polymorphisms
Imputation of behavioral candidate gene repeat variants in 486,551 publicly-available UK Biobank individuals
European Journal of Human Genetics (2019)
Translational Psychiatry (2019)
Journal of Neural Transmission (2019)