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For these analyses, a subset of participants from the parent study completed an online survey of TD. A total of 548 eligible subjects completed the online survey (81.9% response rate). Individuals who reported volitional sunbathing or indoor tanning completed three TD scales to assess lifetime TD: the modified CAGE [5, 11], the modified DSM-IV-TR [5, 11] and the Indoor Tanning Affect and Pathology Scale (iTAPS), a new scale developed by one of the authors (JS) to capture dependence symptoms specifically suggestive of an opioid-like model of TD [http://www.selleckchem.com/products/Y-27632.html Y-27632 cell line] (i.e. loss of control, craving, withdrawal, stress relief and mood enhancement related to tanning) [2]. Participants were classified as TD if they were positively identified as TD on all three TD scales (n?=?79) or not TD if they were negative for TD on all three scales (n?=?213). This restrictive classification based on multiple scales was used to identify the most homogeneous phenotypes (TD vs. not TD) and increase power. See Figure S1 for the flow of participants in the study. DNA from saliva samples was quantified using a Hoefer DyNA Quant 200 fluorometer and arrayed at a concentration of 10?ng/��l for analysis on Axiom Exome 319 Array Plates from Affymetrix (http://www.affymetrix.com). In the exome-wide analysis, one gene, [http://www.selleckchem.com/products/chir-99021-ct99021-hcl.html CHIR-99021 supplier] patched domain containing 2 (PTCHD2), yielded a statistically significant P-value of 2.5?��?10?6 on the gene-based burden analysis after Bonferroni correction (OR?=?0.27) (Table?1). We observed significantly fewer individuals who were TD with a minor allele in this gene compared to individuals who were classified as not TD. Details of the variants are shown in Table S1. Aldehyde dehydrogenase 1 family member B1 (ALDH1B1) was the second highest gene associated with TD; the association was not statistically significant with correction for multiple comparisons. Other top genes in the gene burden analysis are presented in Table?1. Of the 35 SNPs which passed QC and had a MAF >0.01 in the ten genes in the candidate gene analysis, four SNPs had a P-value [https://en.wikipedia.org/wiki/Fleroxacin Fleroxacin] for multiple comparisons (Table?2). No individual SNP surpassed the Bonferroni corrected exome-wide significance threshold, but the most significant single SNP, rs861204, a missense variant mapped to transmembrane (C-terminal) protease, serine 12 (TMPRSS12), had a P-value of 4.10?��?10?5 (OR?=?2.29). All SNPs with a P-value