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Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis

Published online by Cambridge University Press:  09 December 2014

K. L. Musliner ,
F. Seifuddin ,
J. A. Judy ,
M. Pirooznia ,
F. S. Goes  and
P. P. Zandi
K. L. Musliner*
Affiliation:
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
F. Seifuddin
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Institute of Medicine, Baltimore, MD, USA
J. A. Judy
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Institute of Medicine, Baltimore, MD, USA
M. Pirooznia
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Institute of Medicine, Baltimore, MD, USA
F. S. Goes
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Institute of Medicine, Baltimore, MD, USA
P. P. Zandi
Affiliation:
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
*
*Address for correspondence: K. L. Musliner, M.P.H., Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 624 N Broadway, Baltimore, MD 21205, USA. (Email: [email protected])
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Abstract

Background.

Previous studies suggest that the relationship between genetic risk and depression may be moderated by stressful life events (SLEs). The goal of this study was to assess whether SLEs moderate the association between polygenic risk of major depressive disorder (MDD) and depressive symptoms in older adults.

Method.

We used logistic and negative binomial regressions to assess the associations between polygenic risk, SLEs and depressive symptoms in a sample of 8761 participants from the Health and Retirement Study. Polygenic scores were derived from the Psychiatric Genomics Consortium genome-wide association study of MDD. SLEs were operationalized as a dichotomous variable indicating whether participants had experienced at least one stressful event during the previous 2 years. Depressive symptoms were measured using an eight-item Center for Epidemiologic Studies Depression Scale subscale and operationalized as both a dichotomous and a count variable.

Results.

The odds of reporting four or more depressive symptoms were over twice as high among individuals who experienced at least one SLE (odds ratio 2.19, 95% confidence interval 1.86–2.58). Polygenic scores were significantly associated with depressive symptoms (β = 0.21, p ⩽ 0.0001), although the variance explained was modest (pseudo r2 = 0.0095). None of the interaction terms for polygenic scores and SLEs was statistically significant.

Conclusions.

Polygenic risk and SLEs are robust, independent predictors of depressive symptoms in older adults. Consistent with an additive model, we found no evidence that SLEs moderated the association between common variant polygenic risk and depressive symptoms.

Keywords

Depressiongeneticspolygenic score analysisstress
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 8 , June 2015 , pp. 1709 - 1720
Copyright
Copyright © Cambridge University Press 2014 

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References

1000 Genomes Project Consortium et al. (2012). An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56–65.Google Scholar
Altshuler, DM, Gibbs, RA, Peltonen, L, Dermitzakis, E, Schaffner, SF, Yu, F, Bonnen, PE, de Bakker, PI, Deloukas, P, Gabriel, SB, Gwilliam, R, Hunt, S, Inouye, M, Jia, X, Palotie, A, Parkin, M, Whittaker, P, Chang, K, Hawes, A, Lewis, LR (2010). Integrating common and rare genetic variation in diverse human populations. Nature 467, 52–58.Google Scholar
Bosker, FJ, Hartman, CA, Nolte, IM, Prins, BP, Terpstra, P, Posthuma, D, van Veen, T, Willemsen, G, DeRijk, RH, de Geus, EJ, Hoogendijk, WJ, Sullivan, PF, Penninx, BW, Boomsma, DI, Snieder, H, Nolen, WA (2011). Poor replication of candidate genes for major depressive disorder using genome-wide association data. Molecular Psychiatry 16, 516–532.CrossRefGoogle ScholarPubMed
Brown, GW, Harris, TO (2008). Depression and the serotonin transporter 5-HTTLPR polymorphism: a review and a hypothesis concerning gene–environment interaction. Journal of Affective Disorders 111, 1–12.Google Scholar
Bukh, JD, Bock, C, Vinberg, M, Werge, T, Gether, U, Kessing, LV (2009). Interaction between genetic polymorphisms and stressful life events in first episode depression. Journal of Affective Disorders 119, 107–115.Google Scholar
Caspi, A, Hariri, AR, Holmes, A, Uher, R, Moffitt, TE (2010). Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry 167, 509–527.Google Scholar
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, 386–389.Google Scholar
Center for Inherited Gene Research (2012 a). Quality control report for genotypic data, March 15, 2012. Health and Retirement Study (http://hrsonline.isr.umich.edu/sitedocs/genetics/HRS_QC_REPORT_MAR2012.pdf).Google Scholar
Center for Inherited Gene Research (2012 b). CIDR Health Retirement Study imputation report – 1000 genomes project reference panel, August 14, 2012. Health and Retirement Study (http://hrsonline.isr.umich.edu/sitedocs/genetics/HRS_1000G_IMPUTE2_REPORT_AUG2012.pdf).Google Scholar
Chang, SC, Glymour, MM, Walter, S, Liang, L, Joenen, KC, Tchetgen, EJ, Cornelis, MC, Kawachi, I, Rimm, E, Kubzansky, LD (2014). Genome-wide polygenic scoring for a 14-year long-term average depression phenotype. Brain and Behavior 4, 298–311.Google Scholar
Chatterjee, N, Wheeler, B, Sampson, J, Hartge, P, Chanock, SJ, Park, J (2013). Projecting the performance of risk prediction based on polygenic analyses of genome-wide association studies. Nature Genetics 45, 400–405.Google Scholar
Chen, J, Li, X, McGue, M (2012). Interacting effect of BDNF Val66Met polymorphism and stressful life events on adolescent depression. Genes, Brain and Behavior 11, 958–965.Google Scholar
Conway, CC, Hammen, C, Brennan, PA, Lind, PA, Najman, JM (2010). Interaction of chronic stress with serotonin transporter and catechol-O-methyltransferase polymorphisms in predicting youth depression. Depression and Anxiety 27, 737–745.CrossRefGoogle ScholarPubMed
Conway, CC, Hammen, C, Espejo, EP, Wray, NR, Najman, JM, Brennan, PA (2012). Appraisals of stressful life events as a genetically-linked mechanism in the stress–depression relationship. Cognitive Therapy and Research 36, 338–347.CrossRefGoogle Scholar
Cross-Disorder Group of the Psychiatric Genomics Consortium, Lee, SH, Ripke, S, Neale, BM, Faraone, SV, Purcell, SM, Perlis, RH, Mowry, BJ, Thapar, A, Goddard, ME, Witte, JS, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, OA, Anjorin, A, Anney, R, Anttila, V, Arking, DE, Asherson, P, Azevedo, MH, Backlund, L, Badner, JA, Bailey, AJ, Banaschewski, T, Barchas, JD, Barnes, MR, Barrett, TB, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, SE, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, EB, Black, DW, Blackwood, DH Bloss, CS, Boehnke, M, Boomsma, DI, Breen, G, Breuer, R, Bruggeman, R, Cormican, P, Buccola, NG, Buitelaar, JK, Bunney, WE, Buxbaum, JD, Byerley, WF, Byrne, EM, Caesar, S, Cahn, W, Cantor, RM, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Cloninger, CR, Collier, DA, Cook, EH, Coon, H, Cormand, B, Corvin, A, Coryell, WH, Craig, DW, Craig, IW, Crosbie, J, Cuccaro, ML, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, De Geus, EJ, Degenhardt, F, Djurovic, S, Donohoe, GJ, Doyle, AE, Duan, J, Dudbridge, F, Duketis, E, Ebstein, RP, Edenberg, HJ, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, AE, Ferrier, IN, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, NB, Freitag, CM, Friedl, M, Frisén, L, Gallagher, L, Gejman, PV, Georgieva, L, Gershon, ES, Geschwind, DH, Giegling, I, Gill, M, Gordon, SD, Gordon-Smith, K, Green, EK, Greenwood, TA, Grice, DE, Gross, M, Grozeva, D, Guan, W, Gurling, H, De Haan, L, Haines, JL, Hakonarson, H, Hallmayer, J, Hamilton, SP, Hamshere, ML, Hansen, TF, Hartmann, AM, Hautzinger, M, Heath, AC, Henders, AK, Herms, S, Hickie, IB, Hipolito, M, Hoefels, S, Holmans, PA, Holsboer, F, Hoogendijk, WJ, Hottenga, JJ, Hultman, CM, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, EG, Jones, I, Jones, L, Tzeng, JY, Kähler, AK, Kahn, RS, Kandaswamy, R, Keller, MC, Kennedy, JL, Kenny, E, Kent, L, Kim, Y, Kirov, GK, Klauck, SM, Klei, L, Knowles, JA, Kohli, MA, Koller, DL, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landén, M, Långström, N, Lathrop, M, Lawrence, J, Lawson, WB, Leboyer, M, Ledbetter, DH, Lee, PH, Lencz, T, Lesch, KP, Levinson, DF, Lewis, CM, Li, J, Lichtenstein, P, Lieberman, JA, Lin, DY, Linszen, DH, Liu, C, Lohoff, FW, Loo, SK, Lord, C, Lowe, JK, Lucae, S, MacIntyre, DJ, Madden, PA, Maestrini, E, Magnusson, PK, Mahon, PB, Maier, W, Malhotra, AK, Mane, SM, Martin, CL, Martin, NG, Mattheisen, M, Matthews, K, Mattingsdal, M, McCarroll, SA, McGhee, KA, McGough, JJ, McGrath, PJ, McGuffin, P, McInnis, MG, McIntosh, A, McKinney, R, McLean, AW, McMahon, FJ, McMahon, WM, McQuillin, A, Medeiros, H, Medland, SE, Meier, S, Melle, I, Meng, F, Meyer, J, Middeldorp, CM, Middleton, L, Milanova, V, Miranda, A, Monaco, AP, Montgomery, GW, Moran, JL, Moreno-De-Luca, D, Morken, G, Morris, DW, Morrow, EM, Moskvina, V, Muglia, P, Mühleisen, TW, Muir, WJ, Müller-Myhsok, B, Murtha, M, Myers, RM, Myin-Germeys, I, Neale, MC, Nelson, SF, Nievergelt, CM, Nikolov, I, Nimgaonkar, V, Nolen, WA, Nöthen, MM, Nurnberger, JI, Nwulia, EA, Nyholt, DR, O'Dushlaine, C, Oades, RD, Olincy, A, Oliveira, G, Olsen, L, Ophoff, RA, Osby, U, Owen, MJ, Palotie, A, Parr, JR, Paterson, AD, Pato, CN, Pato, MT, Penninx, BW, Pergadia, ML, Pericak-Vance, MA, Pickard, BS, Pimm, J, Piven, J, Posthuma, D, Potash, JB, Poustka, F, Propping, P, Puri, V, Quested, DJ, Quinn, EM, Ramos-Quiroga, JA, Rasmussen, HB, Raychaudhuri, S, Rehnström, K, Reif, A, Ribasés, M, Rice, JP, Rietschel, M, Roeder, K, Roeyers, H, Rossin, L, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, AR, Sanders, SJ, Santangelo, SL, Sergeant, JA, Schachar, R, Schalling, M, Schatzberg, AF, Scheftner, WA, Schellenberg, GD, Scherer, SW, Schork, NJ, Schulze, TG, Schumacher, J, Schwarz, M, Scolnick, E, Scott, LJ, Shi, J, Shilling, PD, Shyn, SI, Silverman, JM, Slager, SL, Smalley, SL, Smit, JH, Smith, EN, Sonuga-Barke, EJ, St Clair, D, State, M, Steffens, M, Steinhausen, HC, Strauss, JS, Strohmaier, J, Stroup, TS, Sutcliffe, JS, Szatmari, P, Szelinger, S, Thirumalai, S, Thompson, RC, Todorov, AA, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, EJ, Van Grootheest, G, Van Os, J, Vicente, AM, Vieland, VJ, Vincent, JB, Visscher, PM, Walsh, CA, Wassink, TH, Watson, SJ, Weissman, MM, Werge, T, Wienker, TF, Wijsman, EM, Willemsen, G, Williams, N, Willsey, AJ, Witt, SH, Xu, W, Young, AH, Yu, TW, Zammit, S, Zandi, PP, Zhang, P, Zitman, FG, Zöllner, S; International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Devlin, B, Kelsoe, JR, Sklar, P, Daly, MJ, O'Donovan, MC, Craddock, N, Sullivan, PF, Smoller, JW, Kendler, KS, Wray, NR (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45, 984–995.Google Scholar
Demirkan, A, Penninx, BW, Hek, K, Wray, NR, Amin, N, Aulchenko, YS, van Dyck, R, de Geus, EJ, Hofman, A, Uitterlinden, AG, Hottenga, J, Nolen, WA, Oostra, BA, Sullivan, PF, Willemsen, G, Zitman, FG, Tiemeier, H, Janssens, AC, Boomsma, DI, van Duijn, CM, Middeldorp, CM (2011). Genetic risk profiles for depression and anxiety in adult and elderly cohorts. Molecular Psychiatry 16, 773–783.Google Scholar
Dudbridge, F (2013). Power and predictive accuracy of polygenic risk scores. PLOS Genetics 9, e1003348.Google Scholar
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, 1041–1049.Google Scholar
Elovainio, M, Kokela, M, Kivimaki, M, Pulkki-Raback, L, Lehtimaki, T, Airla, N, Keltikangas-Jarvinen, L (2007). Genetic variants in the DRD2 gene moderate the relationship between stressful life events and depressive symptoms in adults: Cardiovascular Risk in Young Finns study. Psychosomatic Medicine 69, 391–395.Google Scholar
Freeman, C, Marchini, J (2007). GTOOL (http://www.well.ox.ac.uk/~cfreeman/software/gwas/gtool.html#Contact). Accessed 20 September 2014.Google Scholar
Hammen, C (1991). Generation of stress in the course of unipolar depression. Journal of Abnormal Psychology 100, 555–561.Google Scholar
Hammen, C (2006). Stress generation in depression: reflections on origins, research, and future directions. Journal of Clinical Psychology 62, 1065–1082.Google Scholar
Health and Retirement Study (2004). HRS 2000 Core, Final V1.0, public use dataset. Produced and distributed by the University of Michigan with funding from The National Institute on Aging (grant number NIA U01AG009740). University of Michigan: Ann Arbor, MI.Google Scholar
Hek, K, Demirkan, A, Lahti, J, Terracciano, A, Teumer, A, Cornelis, MC, Amin, N, Bakshis, E, Baumert, J, Ding, J, Liu, Y, Marciante, K, Meirelles, O, Nalls, MA, Sun, YV, Vogelzangs, N, Yu, L, Bandinelli, S, Benjamin, EJ, Bennett, DA, Boomsma, D, Cannas, A, Coker, LH, de Geus, E, De Jager, PL, Diez-Roux, A, Purcell, S, Hu, FB, Rimm, EB, Hunter, DJ, Jensen, MK, Curhan, G, Rice, K, Penman, AD, Rotter, JI, Sotoodehnia, N, Emeny, R, Eriksson, JG, Evans, DA, Ferrucci, L, Fornage, M, Gudnason, V, Hofman, A, Illig, T, Kardia, S, Kelly-Hayes, M, Koenen, K, Kraft, P, Kuningas, M, Massaro, JM, Melzer, D, Mulas, A, Mulder, CL, Murray, A, Oostra, BA, Palotie, A, Penninx, B, Petersmann, A, Pilling, LC, Psaty, B, Rawal, R, Reiman, EM, Schulz, A, Shulman, JM, Singleton, AB, Smith, AV, Sutin, AR, Uitterlinden, AG, Völzke, H, Widen, E, Yaffe, K, Zonderman, AB, Cucca, F, Harris, T, Ladwig, K, Llewellyn, DJ, Räikkönen, K, Tanaka, T, van Duijn, CM, Grabe, HJ, Launer, LJ, Lunetta, KL, Mosley, TH Jr, Newman, AB, Tiemeier, H, Murabito, J (2013). A genome-wide association study of depressive symptoms. Biological Psychiatry 73, 667–678.CrossRefGoogle ScholarPubMed
Holmes, TH, Rahe, RH (1967). The social readjustment rating scale. Journal of Psychosomatic Research 11, 213–221.Google Scholar
Hosang, GM, Shiles, C, Tansey, KE, KcGuffin, P, Uher, R (2014). Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta analysis. BMC Medicine 12, 7.Google Scholar
Ingram, RE, Luxton, DD (2005). Vulnerability-stress models. In Development of Psychopathology: a Vulnerability-Stress Perspective (ed. Hankin, B. L. and Abela, J. R.), pp. 32–46. Sage Publications, Inc.: Thousand Oaks, CA. Google Scholar
International Schizophrenia Consortium (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752.CrossRefGoogle Scholar
Ising, M, Lucrae, S, Binder, EB, Bettecken, T, Uhr, M, Ripke, S, Kohli, MA, Hennings, JM, Horstmann, S, Kloiber, S, Menke, A, Bondy, B, Rupprecht, R, Domschke, K, Baune, BT, Arolt, V, Rush, JA, Holsboer, F, Muller-Myhsok, B (2009). A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression. Archives of General Psychiatry 66, 966–975.CrossRefGoogle ScholarPubMed
Juhasz, G, Hullam, G, Eszlari, N, Gonda, X, Antal, P, Anderson, IM, Hokfelt, TG, Deakin, JF, Bagdy, G (2014). Brain galanin system genes interact with life stresses in depression-related phenotypes. Proceedings of the National Academy of Sciences 111, E1666–E1673.Google Scholar
Juster, FT, Suzman, R (1995). An overview of the health and retirement study. Journal of Human Resources 30, S7–S56.Google Scholar
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, 444–454.Google Scholar
Kaufman, J, Yang, BZ, Douglas-Palumberi, H, Grasso, D, Lipschitz, D, Houshyar, S, Krystal, JH, Gelernter, J (2006). Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry 59, 673–680.Google Scholar
Keller, MC (2014). Gene × environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution. Biological Psychiatry 75, 18–24.Google Scholar
Kendler, KS (2001). Twin studies of psychiatric illness: an update. Archives of General Psychiatry 58, 1005–1014.Google Scholar
Kendler, KS, Baker, JH (2007). Genetic influences on measures of the environment: a systematic review. Psychological Medicine 37, 615–626.Google Scholar
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, 539–547.Google Scholar
Kendler, KS, Kessler, RC, Walters, EE, MacLean, C, Neale, MC, Heath, AC, Eaves, LJ (1995). Stressful life events, genetic liability, and onset of an episode of major depression in women. American Journal of Psychiatry 152, 833–842.Google Scholar
Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR, Walters, EE (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 593–602.Google Scholar
Kim, JM, Stewart, R, Kim, SW, Yang, SJ, Shin, IS, Kim, YH, Yoon, JS (2007). Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biological Psychiatry 62, 423–428.Google Scholar
Levinson, DF, Mostafavi, S, Milaneschi, Y, Rivera, M, Ripke, S, Wray, NR, Sullivan, PF (2014). Genetic studies of major depressive disorder: why are there no genome-wide association study findings and what can we do about it? Biological Psychiatry 76, 510–512.Google Scholar
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, 949–957.Google Scholar
Liu, RT, Alloy, LB (2010). Stress generation in depression: a systematic review of the empirical literature and recommendations for future study. Clinical Psychology Review 30, 582–593.Google Scholar
Liu, Z, Liu, W, Yao, L, Yang, C, Xiao, L, Wan, Q, Gao, K, Wang, H, Zhu, F, Wang, G, Xiao, Z (2013). Negative life events and corticotropin-releasing-hormone receptor1 gene in recurrent major depressive disorder. Scientific Reports 3, 1548.Google Scholar
Luan, JA, Wong, MY, Day, NE, Wareham, NJ (2001). Sample size determination for studies of gene–environment interaction. International Journal of Epidemiology 30, 1035–1040.CrossRefGoogle ScholarPubMed
Major Depressive Disorder Work Group of the Psychiatric GWAS Consortium, 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, Müller-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, Völzke, 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, 497–511.Google ScholarPubMed
Mandelli, L, Serretti, A, Marino, E, Pirovano, A, Calati, R, Colombo, C (2007). Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders. International Journal of Neuropsychopharmacology 10, 437–447.Google Scholar
Middeldorp, CM, Cath, DC, Beem, AL, Willemsen, G, Boomsma, DI (2008). Life events, anxious depression and personality: a prospective and genetic study. Psychological Medicine 38, 1557–1565.Google Scholar
Muglia, P, Tozzi, F, Galwey, NW, Francks, C, Upmanyu, R, Kong, XQ, Antoniades, A, Domenici, E, Perry, J, Rothen, S, Vandeleur, CL, Mooser, V, Waeber, G, Vollenweider, P, Preisig, M, Lucae, S, Müller-Myhsok, B, Holsboer, F, Middleton, LT, Roses, AD (2010). Genome-wide association study of recurrent major depressive disorder in two European case–control cohorts. Molecular Psychiatry 15, 589–601.Google Scholar
Munafò, MR, Durrant, C, Lewis, G, Flint, J (2009). Gene × environment interactions at the serotonin transporter locus. Biological Psychiatry 65, 211–219.Google Scholar
Nakatani, D, Sato, H, Sakata, Y, Shiotani, U, Kinjo, K, Mizuno, H, Shimizu, M, Ito, H, Koretsune, Y, Hirayama, A, Hori, M (2005). Influence of serotonin transporter gene polymorphism on depressive symptoms and new cardiac events after acute myocardial infarction. American Heart Journal 150, 652–658.CrossRefGoogle ScholarPubMed
National Institute of Aging (2007). Growing Old in America: The Health and Retirement Study (HRS Databook) (http://hrsonline.isr.umich.edu/index.php?p=dbook). Accessed November 2014.Google Scholar
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, 113–119.Google Scholar
Post, RM (1992). Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. American Journal of Psychiatry 149, 999–1010.Google ScholarPubMed
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, 904–909.Google Scholar
Priess-Groben, H, Hyde, JS (2013). 5-HTTLPR × stress in adolescent depression: moderation by MAOA and gender. Journal of Abnormal Child Psychology 41, 281–294.Google Scholar
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, 559–575.CrossRefGoogle ScholarPubMed
Radloff, LS (1977). The CES-D Scale: a self-report depression scale for research in the general population. Applied Psychological Measurement 1, 385–401.Google Scholar
Rietschel, M, Mattheisen, M, Frank, J, Treutlein, J, Degenhardt, F, Breuer, R, Steffens, M, Mier, D, Esslinger, C, Walter, H, Kirsch, P, Erk, S, Schnell, K, Herms, S, Wichmann, H, Schreiber, S, Jöckel, K, Strohmaier, J, Roeske, D, Haenisch, B, Gross, M, Hoefels, S, Lucae, S, Binder, EB, Wienker, TF, Schulze, TG, Schmäl, C, Zimmer, A, Juraeva, D, Brors, B, Bettecken, T, Meyer-Lindenberg, A, Müller-Myhsok, B, Maier, W, Nöthen, M, Cichon, S (2010). Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression. Biological Psychiatry 68, 578–585.Google Scholar
Risch, N, Herrell, R, Lehner, T, Liang, K, 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, 2462–2471.Google Scholar
Shi, J, Potash, JB, Knowles, JA, Weissman, MM, Coryell, W, Scheftner, WA, Lawson, WB, DePaulo, J, 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, 193–201.Google Scholar
Shyn, SI, Shi, J, Kraft, JB, Potash, JB, Knowles, JA, Weissman, MM, Garriock, HA, Yokoyama, JS, McGrath, PJ, Peters, EJ, Scheftner, WA, Coryell, W, Lawson, WB, Jancic, D, Gejman, PV, Sanders, AR, Holmans, P, Slager, SL, Levinson, DF, Hamilton, SP (2011). Novel loci for major depression identified by genome-wide association study of sequenced treatment alternatives to relieve depression and meta-analysis of three studies. Molecular Psychiatry 16, 202–215.CrossRefGoogle ScholarPubMed
Steffick, DE (2000). Documentation of Affective Functioning Measures in the Health and Retirement Study (http://hrsonline.isr.umich.edu/sitedocs/userg/dr-005.pdf). Accessed 10 March 2013.Google Scholar
Stroud, CB, Davila, J, Moyer, A (2008). The relationship between stress and depression in first onsets versus recurrences: a meta-analytic review. Journal of Abnormal Psychology 117, 206–213.Google Scholar
Sullivan, PF (2010). The Psychiatric GWAS Consortium: big science comes to psychiatry. Neuron 68, 182–186.Google Scholar
Sullivan, PF, Daly, MJ, O'Donovan, M (2012). Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nature Reviews Genetics 13, 537–551.Google Scholar
Sullivan, PF, de Geus, EJ, Willemsen, G, James, MR, Smit, JH, Zandbelt, T, Arolt, V, Baune, BT, Blackwood, D, Cichon, S, Coventry, WL, Domschke, K, Farmer, A, Fava, M, Gordon, SD, He, Q, Heath, AC, Heutink, P, Holsboer, F, Hoogendijk, WJ, Hottenga, JJ, Hu, Y, Kohli, M, Lin, D, Lucae, S, Macintyre, DJ, Maier, W, McGhee, KA, McGuffin, P, Montgomery, GW, Muir, WJ, Nolen, WA, Nöthen, MM, Perlis, RH, Pirlo, K, Posthuma, D, Rietschel, M, Rizzu, P, Schosser, A, Smit, AB, Smoller, JW, Tzeng, J, van Dyck, R, Verhage, M, Zitman, FG, Martin, NG, Wray, NR, Boomsma, DI, Penninx, BW (2009). Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Molecular Psychiatry 14, 359–375.Google Scholar
Sullivan, PF, Neale, MC, Kendler, KS (2000). Genetic epidemiology of major depression: review and meta-analysis. American Journal of Psychiatry 157, 1552–1562.Google Scholar
Terracciano, A, Tanaka, T, Sutin, AR, Sanna, S, Deiana, B, Lai, S, Uda, M, Schlessinger, D, Abecasis, GR, Ferrucci, L, Costa, PT (2010). Genome-wide association scan of trait depression. Biological Psychiatry 68, 811–817.Google Scholar
Turvey, CL, Wallace, RB, Herzog, R (1999). A revised CES-D measure of depressive symptoms and a DSM-based measure of major depressive episodes in the elderly. International Psychogeriatrics 11, 139–148.Google Scholar
Uher, R, McGuffin, P (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry 15, 18–22.CrossRefGoogle ScholarPubMed
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, 36–48.Google Scholar
Zheng, J, Li, Y, Abecasis, GR, Scheet, P (2011). Comparison of approaches to account for uncertainty in analysis if imputed genotypes. Genetic Epidemiology 35, 102–110.Google Scholar
Zimmermann, P, Bruckl, T, Nocon, A, Pfister, H, Binder, EB, Uhr, M, Lieb, R, Moffitt, TE, Caspi, A, Holsboer, F, Ising, M (2011). Interaction of FKBP5 gene variants and adverse life events in predicting depression onset: results from a 10-year prospective community study. American Journal of Psychiatry 168, 1107–1116.Google Scholar
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