METHODS: Opioid dependent PWID were interviewed and tested for HIV and HCV in five Ukrainian cities from January 2014 to March 2015. Logistic regression was used to examine the independent correlates of two cascade steps: a) anti-HCV positive status awareness; b) chronic HCV confirmation; and of c) annual HCV testing for PWID.
RESULTS: Among 1613 PWID, 1002 (62.1%) had anti-HCV positive test result, of which 568 (56.7%) were aware of it before the study and 346 (34.5%) reported previous confirmatory testing for chronic HCV. Independent correlates of being aware they had anti-HCV positivity included: current [AOR: 3.08; 95%CI: 2.16-4.40] or prior [AOR: 1.85; 95%CI: 1.27-2.68] opioid agonistic treatment (OAT) experience, relative to no prior OAT, living in Lviv [AOR: 0.50; 95%CI: 0.31-0.81] or Odesa [AOR: 2.73; 95%CI: 1.51-4.93] relative to Kyiv and being aware of having HIV [AOR: 4.10; 95%CI: 2.99-5.62]. Independent correlates of confirming HCV infection among those who were aware of their anti-HCV positive status included: current OAT [AOR: 2.00; 95%CI: 1.24-3.23], relative to prior OAT, the middle income category [AOR: 1.74, 95%CI: 1.15-2.63], relative to the lowest, and receiving ART [AOR: 4.54; 95%CI: 2.85-7.23]. Among 1613 PWID, 918 (56.9%) were either HCV negative or not aware of their HCV positive status, of which 198 (21.6%) reported recent anti-HCV test (during last 12 month). Recent anti-HCV test in this group was associated with current [AOR: 7.17; 95%CI: 4.63-11.13] or prior [AOR: 2.24; 95%CI: 1.32-3.81] OAT experience, relative to no prior OAT.
CONCLUSION: Encouraging PWID to participate in OAT may be an effective strategy to diagnose and link PWID who are HCV positive to care. Among HIV negative participants, regular HCV testing may be ensured by participation in OAT. More studies are needed to assess HCV treatment utilization among PWID in Ukraine and OAT as a possible way to retain them in treatment.
METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4).
RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99).
CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.
METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.
RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.
CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.