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Chunk #5 — INTRODUCTION

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Do 5HTTLPR and stress interact in risk for depression and suicidality? Item response analyses of a large sample.
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Here we explore the association of 5HTTLPR genotype and its interaction with SLE on risk of depression or suicidality in a large sample of 3,243 individuals from 2,230 twin families, which include the 824 MZ pairs previously analyzed. Among the 14 attempts to replicate the original report [Munafo et al., 2008], only 1 [Surtees et al., 2006] has been larger (N = 4,175) than ours. The remainder had fewer than 1,100 subjects while five studies had fewer than 200. Munafo et al. 2008 investigated the power to detect 5HTTLPR interaction effects using simulation, varying the sizes of main and interaction effects, and concluded that samples of several thousand are needed. Our analyses are conducted (1) for the full data set and (2) for a data set restricted to replicate, as closely as possible, the data structure and analyses of Caspi et al. [2003]. In addition, we genotyped the rs25531 SNP to assess whether it further refines any association with 5HTTLPR. In human studies of this polymorphism's association with neurological activity both S-dominant [Lesch et al., 1996; Hranilovic et al., 2004;