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Polygenic interactions with environmental adversity in the aetiology of major depressive disorder

  • N. Mullins (a1), R. A. Power (a1), H. L. Fisher (a1), K. B. Hanscombe (a2), J. Euesden (a1), R. Iniesta (a1), D. F. Levinson (a3), M. M. Weissman (a4), J. B. Potash (a5), J. Shi (a6), R. Uher (a1) (a7), S. Cohen-Woods (a8), M. Rivera (a1) (a9), L. Jones (a10), I. Jones (a11), N. Craddock (a11), M. J. Owen (a11), A. Korszun (a12), I. W. Craig (a1), A. E. Farmer (a1), P. McGuffin (a1), G. Breen (a1) (a13) and C. M. Lewis (a1) (a2)...
Abstract
Background

Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.

Method

The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.

Results

PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.

Conclusions

CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

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Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
*Address for correspondence: N. Mullins, M.Sc., MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK. (Email: Niamh.mullins@kcl.ac.uk)
References
Hide All
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). American Psychiatric Association: Washington, DC.
Battle A, Mostafavi S, Zhu X, Potash JB, Weissman MM, McCormick C, Haudenschild CD, Beckman KB, Shi J, Mei R, Urban AE, Montgomery SB, Levinson DF, Koller D (2014). Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals. Genome Research 24, 1424.
Beck AT, Steer RA, Brown GK (1996). Beck Depression Inventory – Second Edition Manual. The Psychological Corporation: San Antonio, TX.
Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W (2003). Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse and Neglect 27, 169190.
Brown GW, Ban M, Craig TK, Harris TO, Herbert J, Uher R (2013). Serotonin transporter length polymorphism, childhood maltreatment, and chronic depression: a specific gene–environment interaction. Depression and Anxiety 30, 513.
Brown GW, Harris TO (1978). Social Origins of Depression: A Study of Psychiatric Disorder in Women. Tavistock: London.
Brugha T, Bebbington B, Tennant C, Hurry J (1985). The List of Threatening Experiences: a subset of 12 life event categories with considerable long-term contextual threat. Psychological Medicine 15, 189194.
Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386389.
Cohen-Woods S, Craig I, Gaysina D, Gray J, Gunasinghe C, Craddock N, Elkin A, Jones L, Kennedy J, King N, Korszun A, Knight J, Owen M, Parikh S, Strauss J, Sterne A, Tozzi F, Perry J, Muglia P, Vincent J, McGuffin P, Farmer A (2010). The Bipolar Association Case–Control Study (BACCS) and meta-analysis: no association with the 5,10-methylenetetrahydrofolate reductase gene and bipolar disorder. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 153B, 12981304.
Cohen-Woods S, Gaysina D, Craddock N, Farmer A, Gray J, Gunasinghe C, Hoda F, Jones L, Knight J, Korszun A, Owen MJ, Sterne A, Craig IW, McGuffin P (2009). Depression Case Control (DeCC) Study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder. Human Molecular Genetics 18, 15041509.
CONVERGE Consortium (2015). Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature 523, 588591.
Dudbridge F (2013). Power and predictive accuracy of polygenic risk scores. PLoS Genetics 9, e1003348.
Duncan LE, Keller MC (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry 168, 10411049.
Farmer A, Breen G, Brewster S, Craddock N, Gill M, Korszun A, Maier W, Middleton L, Mors O, Owen M, Perry J, Preisig M, Rietschel M, Reich T, Jones L, Jones I, McGuffin P (2004). The Depression Network (DeNT) Study: methodology and sociodemographic characteristics of the first 470 affected sibling pairs from a large multi-site linkage genetic study. BMC Psychiatry 4, 42.
Fisher HL, Cohen-Woods S, Hosang GM, Korszun A, Owen M, Craddock N, Craig IW, Farmer AE, McGuffin P, Uher R (2013). Interaction between specific forms of childhood maltreatment and the serotonin transporter gene (5-HTT) in recurrent depressive disorder. Journal of Affective Disorders 145, 136141.
Fisher HL, Cohen-Woods S, Hosang GM, Uher R, Powell-Smith G, Keers R, Tropeano M, Korszun A, Jones L, Jones I, Owen M, Craddock N, Craig IW, Farmer AE, McGuffin P (2012). Stressful life events and the serotonin transporter gene (5-HTT) in recurrent clinical depression. Journal of Affective Disorders 136, 189193.
Flint J, Kendler KS (2014). The genetics of major depression. Neuron 81, 484503.
Freeman B, Smith N, Curtis C, Huckett L, Mill J, Craig IW (2003). DNA from buccal swabs recruited by mail: evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping. Behavior Genetics 33, 6772.
Gauderman WJ, Morrison JM (2009). QUANTO 1.2.4: A computer program for power and sample size calculations for genetic–epidemiology studies. University of Southern California: Los Angeles, CA (http://biostats.usc.edu/Quanto.html).
Gaysina D, Cohen-Woods S, Chow PC, Martucci L, Schosser A, Ball HA, Tozzi F, Perry J, Muglia P, Craig IW, McGuffin P, Farmer A (2009). Association of the dystrobrevin binding protein 1 gene (DTNBP1) in a bipolar case–control study (BACCS). American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 150B, 836844.
Karg K, Burmeister M, Shedden K, Sen S (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Archives of General Psychiatry 68, 444454.
Keers R, Uher R, Huezo-Diaz P, Smith R, Jaffee S, Rietschel M, Henigsberg N, Kozel D, Mors O, Maier W, Zobel A, Hauser J, Souery D, Placentino A, Larsen ER, Dmitrzak-Weglarz M, Gupta B, Hoda F, Craig I, McGuffin P, Farmer AE, Aitchison KJ (2011). Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project. Pharmacogenomics Journal 11, 138145.
Keller MC (2014). Gene x environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution. Biological Psychiatry 75, 1824.
Kendler KS, Karkowski LM, Prescott CA (1999). Causal relationship between stressful life events and the onset of major depression. American Journal of Psychiatry 156, 837841.
Kendler KS, Karkowski-Shuman L (1997). Stressful life events and genetic liability to major depression: genetic control of exposure to the environment? Psychological Medicine 27, 539547.
Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ (1993). The lifetime history of major depression in women. Reliability of diagnosis and heritability. Archives of General Psychiatry 50, 863870.
Kessler RC (1997). The effects of stressful life events on depression. Annual Review of Psychology 48, 191214.
Kessler RC, Davis CG, Kendler KS (1997). Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey. Psychological Medicine 27, 11011119.
Lewis CM, Ng MY, Butler AW, Cohen-Woods S, Uher R, Pirlo K, Weale ME, Schosser A, Paredes UM, Rivera M, Craddock N, Owen MJ, Jones L, Jones I, Korszun A, Aitchison KJ, Shi J, Quinn JP, Mackenzie A, Vollenweider P, Waeber G, Heath S, Lathrop M, Muglia P, Barnes MR, Whittaker JC, Tozzi F, Holsboer F, Preisig M, Farmer AE, Breen G, Craig IW, McGuffin P (2010). Genome-wide association study of major recurrent depression in the U.K. population. American Journal of Psychiatry 167, 949957.
McGuffin P, Katz R, Aldrich J (1986). Past and Present State Examination: the assessment of ‘lifetime ever’ psychopathology. Psychological Medicine 16, 461465.
Motrico E, Moreno-Kustner B, de Dios Luna J, Torres-Gonzalez F, King M, Nazareth I, Monton-Franco C, Gilde Gomez-Barragan MJ, Sanchez-Celaya M, Diaz-Barreiros MA, Vicens C, Moreno-Peral P, Bellon JA (2013). Psychometric properties of the List of Threatening Experiences – LTE and its association with psychosocial factors and mental disorders according to different scoring methods. Journal of Affective Disorders 150, 931940.
Musliner KL, Seifuddin F, Judy JA, Pirooznia M, Goes FS, Zandi PP (2015). Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis. Psychological Medicine 45, 17091720.
Nagelkerke NJ (1991). A note on a general definition of the coefficient of determination. Biometrika 78, 691692.
Nanni V, Uher R, Danese A (2012). Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. American Journal of Psychiatry 169, 141151.
Nelson EC, Heath AC, Madden PA, Cooper ML, Dinwiddie SH, Bucholz KK, Glowinski A, McLaughlin T, Dunne MP, Statham DJ, Martin NG (2002). Association between self-reported childhood sexual abuse and adverse psychosocial outcomes: results from a twin study. Archives of General Psychiatry 59, 139145.
Peyrot WJ, Milaneschi Y, Abdellaoui A, Sullivan PF, Hottenga JJ, Boomsma DI, Penninx BW (2014). Effect of polygenic risk scores on depression in childhood trauma. British Journal of Psychiatry 205, 113119.
Power RA, Wingenbach T, Cohen-Woods S, Uher R, Ng MY, Butler AW, Ising M, Craddock N, Owen MJ, Korszun A, Jones L, Jones I, Gill M, Rice JP, Maier W, Zobel A, Mors O, Placentino A, Rietschel M, Lucae S, Holsboer F, Binder EB, Keers R, Tozzi F, Muglia P, Breen G, Craig IW, Muller-Myhsok B, Kennedy JL, Strauss J, Vincent JB, Lewis CM, Farmer AE, McGuffin P (2013). Estimating the heritability of reporting stressful life events captured by common genetic variants. Psychological Medicine 43, 19651971.
Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006). Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics 38, 904909.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007). PLINK: a tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics 81, 559575.
Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748752.
Ripke S, Wray NR, Lewis CM, Hamilton SP, Weissman MM, Breen G, Byrne EM, Blackwood DH, Boomsma DI, Cichon S, Heath AC, Holsboer F, Lucae S, Madden PA, Martin NG, McGuffin P, Muglia P, Noethen MM, Penninx BP, Pergadia ML, Potash JB, Rietschel M, Lin D, Muller-Myhsok B, Shi J, Steinberg S, Grabe HJ, Lichtenstein P, Magnusson P, Perlis RH, Preisig M, Smoller JW, Stefansson K, Uher R, Kutalik Z, Tansey KE, Teumer A, Viktorin A, Barnes MR, Bettecken T, Binder EB, Breuer R, Castro VM, Churchill SE, Coryell WH, Craddock N, Craig IW, Czamara D, De Geus EJ, Degenhardt F, Farmer AE, Fava M, Frank J, Gainer VS, Gallagher PJ, Gordon SD, Goryachev S, Gross M, Guipponi M, Henders AK, Herms S, Hickie IB, Hoefels S, Hoogendijk W, Hottenga JJ, Iosifescu DV, Ising M, Jones I, Jones L, Jung-Ying T, Knowles JA, Kohane IS, Kohli MA, Korszun A, Landen M, Lawson WB, Lewis G, Macintyre D, Maier W, Mattheisen M, McGrath PJ, McIntosh A, McLean A, Middeldorp CM, Middleton L, Montgomery GM, Murphy SN, Nauck M, Nolen WA, Nyholt DR, O'Donovan M, Oskarsson H, Pedersen N, Scheftner WA, Schulz A, Schulze TG, Shyn SI, Sigurdsson E, Slager SL, Smit JH, Stefansson H, Steffens M, Thorgeirsson T, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Volzke H, Weilburg JB, Willemsen G, Zitman FG, Neale B, Daly M, Levinson DF, Sullivan PF (2013). A mega-analysis of genome-wide association studies for major depressive disorder. Molecular Psychiatry 18, 497511.
Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. Journal of the American Medical Association 301, 24622471.
Rothman KJ, Greenland S, Lash TL (2008). Modern Epidemiology. Wolter Kluwer Health, Lippincott Williams and Wilkins: Philadelphia, PA.
Shi J, Potash JB, Knowles JA, Weissman MM, Coryell W, Scheftner WA, Lawson WB, DePaulo JR Jr., Gejman PV, Sanders AR, Johnson JK, Adams P, Chaudhury S, Jancic D, Evgrafov O, Zvinyatskovskiy A, Ertman N, Gladis M, Neimanas K, Goodell M, Hale N, Ney N, Verma R, Mirel D, Holmans P, Levinson DF (2011). Genome-wide association study of recurrent early-onset major depressive disorder. Molecular Psychiatry 16, 193201.
Silberg J, Pickles A, Rutter M, Hewitt J, Simonoff E, Maes H, Carbonneau R, Murrelle L, Foley D, Eaves L (1999). The influence of genetic factors and life stress on depression among adolescent girls. Archives of General Psychiatry 56, 225232.
Sullivan PF, Neale MC, Kendler KS (2000). Genetic epidemiology of major depression: review and meta-analysis. American Journal of Psychiatry 157, 15521562.
Uher R (2014). Gene–environment interactions in common mental disorders: an update and strategy for a genome-wide search. Social Psychiatry and Psychiatric Epidemiology 49, 314.
Uher R, Caspi A, Houts R, Sugden K, Williams B, Poulton R, Moffitt TE (2011). Serotonin transporter gene moderates childhood maltreatment's effects on persistent but not single-episode depression: replications and implications for resolving inconsistent results. Journal of Affective Disorders 135, 5665.
Uher R, Perroud N, Ng MY, Hauser J, Henigsberg N, Maier W, Mors O, Placentino A, Rietschel M, Souery D, Zagar T, Czerski PM, Jerman B, Larsen ER, Schulze TG, Zobel A, Cohen-Woods S, Pirlo K, Butler AW, Muglia P, Barnes MR, Lathrop M, Farmer A, Breen G, Aitchison KJ, Craig I, Lewis CM, McGuffin P (2010). Genome-wide pharmacogenetics of antidepressant response in the GENDEP project. American Journal of Psychiatry 167, 555564.
Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basanez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabe E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fevre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gosselin R, Grainger R, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Ma J, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O'Donnell M, O'Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA III, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Leon FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng ZJ, Zonies D, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA (2012). Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 21632196.
Wing JK, Babor T, Brugha T, Burke J, Cooper JE, Giel R, Jablenski A, Regier D, Sartorius N (1990). SCAN. Schedules for Clinical Assessment in Neuropsychiatry. Archives of General Psychiatry 47, 589593.
World Health Organization (1993). The ICD-10 Classification of Mental and Behavioural Disorders. Diagnostic Criteria for Research. World Health Organization: Geneva, Switzerland.
Wray NR, Pergadia ML, Blackwood DH, Penninx BW, Gordon SD, Nyholt DR, Ripke S, MacIntyre DJ, McGhee KA, Maclean AW, Smit JH, Hottenga JJ, Willemsen G, Middeldorp CM, de Geus EJ, Lewis CM, McGuffin P, Hickie IB, van den Oord EJ, Liu JZ, Macgregor S, McEvoy BP, Byrne EM, Medland SE, Statham DJ, Henders AK, Heath AC, Montgomery GW, Martin NG, Boomsma DI, Madden PA, Sullivan PF (2012). Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned. Molecular Psychiatry 17, 3648.
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