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

Culverhouse, R. C., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., Burmeister, M., Cohen-Woods, S., Etain, B., Fisher, H. L., Goldman, N., Guillaume, S., Horwood, J., Juhasz, G., Lester, K. J., Mandelli, L., Middeldorp, C. M., Olie, E., Villafuerte, S., Air, T. M., Araya, R., Bowes, L., Burns, R., Byrne, E. M., Coffey, C., Coventry, W. L., Gawronski, K. A. B., Glei, D., Hatzimanolis, A., Hottenga, J. -J., Jaussent, I., Jawahar, C., Jennen-Steinmetz, C., Kramer, J. R., Lajnef, M., Little, K., zu Schwabedissen, H. M., Nauck, M., Nederhof, E., Petschner, P., Peyrot, W. J., Schwahn, C., Sinnamon, G., Stacey, D., Tian, Y., Toben, C., van der Auwera, S., Wainwright, N., Wang, J. -C., Willemsen, G., Anderson, I. M., Arolt, V., Aslund, C., Bagdy, G., Baune, B. T., Bellivier, F., Boomsma, D. I., Courtet, P., Dannlowski, U., de Geus, E. J. C., Deakin, J. F. W., Easteal, S., Eley, T., Fergusson, D. M., Goate, A. M., Gonda, X., Grabe, H. J., Holzman, C., Johnson, E. O., Kennedy, M., Laucht, M., Martin, N. G., Munafo, M. R., Nilsson, K. W., Oldehinkel, A. J., Olsson, C. A., Ormel, J., Otte, C., Patton, G. C., Penninx, B. W. J. H., Ritchie, K., Sarchiapone, M., Scheid, J. M., Serretti, A., Smit, J. H., Stefanis, N. C., Surtees, P. G., Volzke, H., Weinstein, M., Whooley, M., Nurnberger Jr, J. I., Breslau, N. and Bierut, L. J. (2017) Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Molecular Psychiatry, 23 1: 133-142. doi:10.1038/mp.2017.44

Author Culverhouse, R. C.
Saccone, N. L.
Horton, A. C.
Ma, Y.
Anstey, K. J.
Banaschewski, T.
Burmeister, M.
Cohen-Woods, S.
Etain, B.
Fisher, H. L.
Goldman, N.
Guillaume, S.
Horwood, J.
Juhasz, G.
Lester, K. J.
Mandelli, L.
Middeldorp, C. M.
Olie, E.
Villafuerte, S.
Air, T. M.
Araya, R.
Bowes, L.
Burns, R.
Byrne, E. M.
Coffey, C.
Coventry, W. L.
Gawronski, K. A. B.
Glei, D.
Hatzimanolis, A.
Hottenga, J. -J.
Jaussent, I.
Jawahar, C.
Jennen-Steinmetz, C.
Kramer, J. R.
Lajnef, M.
Little, K.
zu Schwabedissen, H. M.
Nauck, M.
Nederhof, E.
Petschner, P.
Peyrot, W. J.
Schwahn, C.
Sinnamon, G.
Stacey, D.
Tian, Y.
Toben, C.
van der Auwera, S.
Wainwright, N.
Wang, J. -C.
Willemsen, G.
Anderson, I. M.
Arolt, V.
Aslund, C.
Bagdy, G.
Baune, B. T.
Bellivier, F.
Boomsma, D. I.
Courtet, P.
Dannlowski, U.
de Geus, E. J. C.
Deakin, J. F. W.
Easteal, S.
Eley, T.
Fergusson, D. M.
Goate, A. M.
Gonda, X.
Grabe, H. J.
Holzman, C.
Johnson, E. O.
Kennedy, M.
Laucht, M.
Martin, N. G.
Munafo, M. R.
Nilsson, K. W.
Oldehinkel, A. J.
Olsson, C. A.
Ormel, J.
Otte, C.
Patton, G. C.
Penninx, B. W. J. H.
Ritchie, K.
Sarchiapone, M.
Scheid, J. M.
Serretti, A.
Smit, J. H.
Stefanis, N. C.
Surtees, P. G.
Volzke, H.
Weinstein, M.
Whooley, M.
Nurnberger Jr, J. I.
Breslau, N.
Bierut, L. J.
Title Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
Publication date 2017-04-04
Year available 2018
Sub-type Article (original research)
DOI 10.1038/mp.2017.44
Open Access Status PMC
Volume 23
Issue 1
Start page 133
End page 142
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1312 Molecular Biology
2738 Psychiatry and Mental health
2804 Cellular and Molecular Neuroscience
Abstract 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.
Keyword Serotonin Transporter Gene
Major Depression
Environment Interaction
Cohort Profile
Life Events
Childhood Maltreatment
Polymorphism 5-Httlpr
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID RC2 MH089951
R01 AA007535
R01 MH081802
K99 DA023549
R37 AA007065
RC2 MH089995
R01 HL079235
R21 DA033827
R01 AA007728
R01 HD042157
P01 CA089392
R01 HD034543
R01 DA026911
P2C HD047879
R01 DA036583
R01 AG016790
U24 MH068457
U01 DP000143
R01 AA010249
R01 AA007065
U10 AA008401
R37 AA007728
R01 AG016661
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 17 Jul 2017, 15:43:56 EST by Anthony Yeates on behalf of Learning and Research Services (UQ Library)