Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Details

• Alternative Title:
  Mol Psychiatry
• Personal Author:
  Culverhouse, Robert C. ; Saccone, Nancy L. ; Horton, Amy C. ; Ma, Yinjiao ; Anstey, Kaarin J. ; Banaschewski, Tobias ; Burmeister, Margit ; Cohen-Woods, Sarah ; Etain, Bruno ; Fisher, Helen L. ; Goldman, Noreen ; Guillaume, Sébastien ; Horwood, John ; Juhasz, Gabriella ; Lester, Kathryn J. ; Mandelli, Laura ; Middeldorp, Christel M. ; Olié, Emilie ; Villafuerte, Sandra ; Air, Tracy M. ; Araya, Ricardo ; Bowes, Lucy ; Burns, Richard ; Byrne, Enda M. ; Coffey, Carolyn ; Coventry, William L. ; Gawronski, Katerina ; Glei, Dana ; Hatzimanolis, Alex ; Hottenga, Jouke-Jan ; Jaussent, Isabelle ; Jawahar, Catharine ; Jennen-Steinmetz, Christine ; Kramer, John R. ; Lajnef, Mohamed ; Little, Keriann ; Meyer zu Schwabedissen, Henriette ; Nauck, Matthias ; Nederhof, Esther ; Petschner, Peter ; Peyrot, Wouter J. ; Schwahn, Christian ; Sinnamon, Grant ; Stacey, David ; Tian, Yan ; Toben, Catherine ; Van der Auwera, Sandra ; Wainwright, Nick ; Wang, Jen-Chyong ; Willemsen, Gonneke ; Anderson, Ian M. ; Arolt, Volker ; Åslund, Cecilia ; Bagdy, Gyorgy ; Baune, Bernhard T. ; Bellivier, Frank ; Boomsma, Dorret I. ; Courtet, Philippe ; Dannlowski, Udo ; de Geus, Eco J.C. ; Deakin, John F. W. ; Easteal, Simon ; Eley, Thalia ; Fergusson, David M. ; Goate, Alison M. ; Gonda, Xenia ; Grabe, Hans J. ; Holzman, Claudia ; Johnson, Eric O. ; Kennedy, Martin ; Laucht, Manfred ; Martin, Nicholas G. ; Munafò, Marcus ; Nilsson, Kent W. ; Oldehinkel, Albertine J. ; Olsson, Craig ; Ormel, Johan ; Otte, Christian ; Patton, George C. ; Penninx, Brenda W.J.H. ; Ritchie, Karen ; Sarchiapone, Marco ; Scheid, JM ; Serretti, Alessandro ; Smit, Johannes H. ; Stefanis, Nicholas C. ; Surtees, Paul G. ; Völzke, Henry ; Weinstein, Maxine ; Whooley, Mary ; Nurnberger, John I. ; Breslau, Naomi ; Bierut, Laura J.
• Description:
  The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.
• Subjects:
  Cooperative Behavior Depression Gene-Environment Interaction Genetic Predisposition To Disease Genotype Humans Life Change Events Serotonin Plasma Membrane Transport Proteins Stress, Psychological
• Source:
  Mol Psychiatry. 23(1):133-142.
• Pubmed ID:
  28373689
• Pubmed Central ID:
  PMC5628077
• Document Type:
  Journal Article
• Funding:
  RC2 MH089951/MH/NIMH NIH HHS/United States ; R01 AA007535/AA/NIAAA NIH HHS/United States ; R01 MH081802/MH/NIMH NIH HHS/United States ; K99 DA023549/DA/NIDA NIH HHS/United States ; R37 AA007065/AA/NIAAA NIH HHS/United States ; RC2 MH089995/MH/NIMH NIH HHS/United States ; R01 HL079235/HL/NHLBI NIH HHS/United States ; R21 DA033827/DA/NIDA NIH HHS/United States ; R01 AA007728/AA/NIAAA NIH HHS/United States ; R01 HD042157/HD/NICHD NIH HHS/United States ; P01 CA089392/CA/NCI NIH HHS/United States ; R01 HD034543/HD/NICHD NIH HHS/United States ; R01 DA026911/DA/NIDA NIH HHS/United States ; P2C HD047879/HD/NICHD NIH HHS/United States ; R01 DA036583/DA/NIDA NIH HHS/United States ; R01 AG016790/AG/NIA NIH HHS/United States ; U24 MH068457/MH/NIMH NIH HHS/United States ; U01 DP000143/DP/NCCDPHP CDC HHS/United States ; R01 AA010249/AA/NIAAA NIH HHS/United States ; R01 AA007065/AA/NIAAA NIH HHS/United States ; Wellcome Trust/United Kingdom ; U10 AA008401/AA/NIAAA NIH HHS/United States ; R37 AA007728/AA/NIAAA NIH HHS/United States ; R01 AG016661/AG/NIA NIH HHS/United States
• Volume:
  23
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:7ec2c473ba9142faa28ec0492d9e56e327ff21ec3083633759ad1e2c5fcf0827
• Download URL:
  https://stacks.cdc.gov/view/cdc/48957/cdc_48957_DS1.pdf
• File Type:
  [PDF - 1.08 MB ]