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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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Supplementary materials

Mullins supplementary material
Mullins supplementary material 1

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188 KB

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