This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Contact me when this article is cited  Related Content  • Related article  • Related letters  • Similar articles in JAMA  Topic Collections  • Occupational and Environmental Medicine  • Psychiatry  • Depression  • Statistics and Research Methods  • Genetics  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

	Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

In Reply: We agree with Drs Koenen and Galea and Drs Lotrich and Lenze regarding the importance of consistent environmental measures in studies of gene-environment interaction. However, it is also important to acknowledge the myriad ways an environmental exposure is defined and potentially adjusted to identify an interaction effect in gene-environment interaction studies when assessing statistical significance. For example, Lotrich and Lenze are critical of our meta-analysis for excluding studies with single heterogeneous life stressors such as job loss, pregnancy, hip fracture, or heart disease. However, exposure to a single life event was not significantly associated with depression in the original study of Caspi et al,¹ in which (as shown in Figure 1 of that article) an interaction with the 5-HTTLPR genotype occurred only among persons with 3 or more stressful life events.

Lotrich and Lenze also fault our analysis for failing to examine the effects of study design (prospective . . . [Full Text of this Article]

Kathleen Ries Merikangas, PhD
kathleen.merikangas@nih.gov

Thomas Lehner, PhD
Genetic Epidemiology Research Branch
National Institute of Mental Health
Bethesda, Maryland

Neil J. Risch, PhD
Institute for Human Genetics
University of California at San Francisco

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Interaction Between the Serotonin Transporter Gene (5-HTTLPR), Stressful Life Events, and Risk of Depression: A Meta-analysis
Neil Risch, Richard Herrell, Thomas Lehner, Kung-Yee Liang, Lindon Eaves, Josephine Hoh, Andrea Griem, Maria Kovacs, Jurg Ott, and Kathleen Ries Merikangas
JAMA. 2009;301(23):2462-2471.
ABSTRACT | FULL TEXT  

RELATED LETTERS

Gene-Environment Interactions and Depression
Karestan C. Koenen and Sandro Galea
JAMA. 2009;302(17):1859-1862.
EXTRACT | FULL TEXT  

Gene-Environment Interactions and Depression
Francis E. Lotrich and Eric Lenze
JAMA. 2009;302(17):1859-1862.
EXTRACT | FULL TEXT  

Gene-Environment Interactions and Depression
Christian Schwahn and Hans Jörgen Grabe
JAMA. 2009;302(17):1859-1862.
EXTRACT | FULL TEXT  

Gene-Environment Interactions and Depression
Nina Rieckmann, Michael A. Rapp, and Jacqueline Müller-Nordhorn
JAMA. 2009;302(17):1859-1862.
EXTRACT | FULL TEXT