Table 2.

Recommendations for Conducting and Reporting GxE Research on Depression in Youth)

Reporting GxE Research	1. Adopt more rigorous reporting standards  (a) Follow STROBE guidelines for reporting observational studies.  (b) Follow STREGA guidelines for reporting genetic studies.
Testing and Reporting GxE Effects
Treatment of the Genotype	2. Make comparisons across all genotype groups (e.g. separately test for the effects of s/s and s/l genotypes).
Reporting Main and Interaction Effects	3. Adopt more thorough reporting standards.  (a) Report all parameters included in the regression model.
	4. Test for main effects with and without the interaction term present depending on hypotheses.  (b) When the interaction term is present, correctly interpret main effects.  (c) Present all data to enable interpretation of interaction effects.
Conducting Formal Tests for Interaction	5. Test for GxE using traditional methods (i.e. cross-product terms).
	6. Incorporate new methods (i.e. test GxE at different values of E).
	7. Report descriptive statistics to enable readers to understand the distribution of genotype and exposures and estimate GxE.
Treatment of Covariates	8. Include all relevant covariates in the analysis, including sex, age, and race/ethnicity.
Reporting Gene-Environment Correlation	9. Test and report gene-environment correlation.
Conceptualizing, Measuring, and Analyzing Depression	10. Use a measure of depressive symptoms as the outcome and note the scale (i.e. additive or multiplicative) used to test GxE.
	11. When diagnostic information is available, use this data to validate results obtained from tests of GxE on symptoms.
	12. Investigate other aspects of depression, including symptom clusters, age at onset vs. course, and comorbidity.
Conceptualizing, Measuring, and Analyzing Environment
Focus on Timing	13. Use more rigorous research designs (i.e. longitudinal, experimental, quasi-experimental).
Examine Frequency and Duration of Exposure	14. Refer to existing reviews on how to conceptualize, measure, and analyze data on life stress and depression.
Poor Measurement and Modeling of Environmental Exposures	15. Use rigorous methods to reliably and validly assess environment and causal associations of “E” to mental health outcomes.
	16. Use more specific methods, rather than indexes or counts, to statistically model aspects of the environment.
Incorporate a Multi-Level Approach	17. Examine how the broader social environment (i.e. schools, neighborhoods) modify genetic effects on depression.
Examine a Wider Array of Proximal Environments	18. Investigate how other proximal environments, such as families and peers, interact with genotypes to influence depression risk.
Increasing Power to Test for GxE	19. Test GxE in larger samples and use more valid and reliable measures of environmental exposures and depressive outcomes.
Improving the Quality of Genetic Data	20. Follow STREGA guidelines for reporting genetic studies and test for Hardy Weinberg Equilibrium (HWE).