Two early reports of G x E effects on psychiatric outcomes, namely 5-HTTLPR and stressful life events on risk of depression, and MAO-A and early childhood maltreatment on conduct disorder, have generated considerable subsequent research investment and controversy.

We propose to attempt to replicate these findings by specifying our analyses to be as close as possible to the original study (the Dunedin sample). ALSPAC is ideally suited to this, being similar to the original study in that it is a prospective cohort study, but considerably larger.

The study team will consist of:

Marcus Munafo

George Davey Smith

Glyn Lewis

Stan Zammit

Anita Thapar

Jon Heron

This group will agree a phenotype specification and analysis plan which most closely matches that of the two original reports which we will seek to replicate, namely:

Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R. Role of genotype in the cycle of violence in maltreated children. Science. 2002 Aug 2;297(5582):851-4.

Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003 Jul 18;301(5631):386-9.

This analysis plan will then be implemented. We believe that this approach will remove the possibility for "significance-chasing", so that any results we obtain will be a true replication (or failure to replicate).

The study team has been chosen to represent those who have been both supportive and critical of psychiatric G x E research.