Australians Of European Ancestry Research Articles

Impact of personal genomic risk information on melanoma prevention behaviors and psychological outcomes: a randomized controlled trial

PurposeWe evaluated the impact of personal melanoma genomic risk information on sun-related behaviors and psychological outcomes.MethodsIn this parallel group, open, randomized controlled trial, 1,025 Australians of European ancestry without melanoma and aged 18–69 years were recruited via the Medicare database (3% consent). Participants were randomized to the intervention (n = 513; saliva sample for genetic testing, personalized melanoma risk booklet based on a 40-variant polygenic risk score, telephone-based genetic counseling, educational booklet) or control (n = 512; educational booklet). Wrist-worn ultraviolet (UV) radiation dosimeters (10-day wear) and questionnaires were administered at baseline, 1 month postintervention, and 12 months postbaseline.ResultsAt 12 months, 948 (92%) participants completed dosimetry and 973 (95%) the questionnaire. For the primary outcome, there was no effect of the genomic risk intervention on objectively measured UV exposure at 12 months, irrespective of traditional risk factors. For secondary outcomes at 12 months, the intervention reduced sunburns (risk ratio: 0.72, 95% confidence interval: 0.54–0.96), and increased skin examinations among women. Melanoma-related worry was reduced. There was no overall impact on general psychological distress.ConclusionPersonalized genomic risk information did not influence sun exposure patterns but did improve some skin cancer prevention and early detection behaviors, suggesting it may be useful for precision prevention. There was no evidence of psychological harm.

Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1

BackgroundNo opioid receptor, mu 1 (OPRM1) gene polymorphisms, including the functional single nucleotide polymorphism (SNP) rs1799971, have been conclusively associated with heroin/other opioid addiction, despite their biological plausibility. We used evidence of polymorphisms altering OPRM1 expression in normal human brain tissue to nominate and then test associations with heroin addiction. MethodsWe tested 103 OPRM1 SNPs for association with OPRM1 messenger RNA expression in prefrontal cortex from 224 European Americans and African Americans of the BrainCloud cohort. We then tested the 16 putative cis-expression quantitative trait loci (cis-eQTL) SNPs for association with heroin addiction in the Urban Health Study and two replication cohorts, totaling 16,729 European Americans, African Americans, and Australians of European ancestry. ResultsFour putative cis-eQTL SNPs were significantly associated with heroin addiction in the Urban Health Study (smallest p = 8.9 × 10−5): rs9478495, rs3778150, rs9384169, and rs562859. Rs3778150, located in OPRM1 intron 1, was significantly replicated (p = 6.3 × 10−5). Meta-analysis across all case-control cohorts resulted in p = 4.3 × 10−8: the rs3778150-C allele (frequency = 16%–19%) being associated with increased heroin addiction risk. Importantly, the functional SNP allele rs1799971-A was associated with heroin addiction only in the presence of rs3778150-C (p = 1.48 × 10−6 for rs1799971-A/rs3778150-C and p = .79 for rs1799971-A/rs3778150-T haplotypes). Lastly, replication was observed for six other intron 1 SNPs that had prior suggestive associations with heroin addiction (smallest p = 2.7 × 10−8 for rs3823010). ConclusionsOur findings show that common OPRM1 intron 1 SNPs have replicable associations with heroin addiction. The haplotype structure of rs3778150 and nearby SNPs may underlie the inconsistent associations between rs1799971 and heroin addiction.

CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection

IL28B polymorphisms strongly predict spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. A recent study proposed a 32-base pair deletion in the CC-chemokine receptor 5 (CCR5) gene (CCR5-Δ32) interacting with the IL28B polymorphisms to influence spontaneous HCV clearance. The aim of this study was to clarify the role of CCR5-Δ32 in treatment-induced clearance of chronic hepatitis C (CHC). A cross-sectional cohort of 813 Caucasian patients with CHC genotype 1 (365 responders and 448 non-responders) who had received standard of care dual therapy with interferon (IFN)-α and ribavirin (RBV) was genotyped for the CCR5-Δ32 and IL28B polymorphisms to examine their interaction with respect to treatment response. CCR5-Δ32 did not influence treatment-induced recovery to IFN-α/RBV in CHC, and did not improve prediction of sustained virological response in the context of the IL28B polymorphisms in a multivariate model. CCR5-Δ32 homozygotes were significantly more frequent in those with CHC than healthy controls in the European cohorts (2.9% vs 0.4%, P<0.0001), but not in Australians of European ancestry. In conclusion, CCR5-Δ32 does not influence treatment response in the context of IL28B polymorphisms. Although CCR5-Δ32 may affect viral clearance within closely controlled geographical and genetic environments, we found no effect in larger cohorts treated with dual therapy.

Increased carotid intima‐media thickness in remote and urban Indigenous Australians: impact of diabetes and components of the metabolic syndrome

Indigenous Australians have rates of cardiovascular (CVD) mortality some seven to 10-fold higher than non-Indigenous Australians aged 25-64 years. We aimed to evaluate the impact of type 2 diabetes and components of the metabolic syndrome on carotid intima-media thickness (CIMT) as a marker of cardiovascular risk in Indigenous Australians living in remote and urban environments and in Australians of European ancestry. CIMT was measured by high-resolution B-mode ultrasound imaging of the common carotid artery in 119 remote Indigenous, 144 urban Indigenous and 122 urban European Australians with and without diabetes. In nondiabetic participants, CIMT was lowest in Europeans (mean (SD) 0.64 mm (0.10)), higher in urban Indigenous Australians (0.67 mm (0.12)) and highest in remote Indigenous Australians (0.73 mm (0.15), P < 0.001). CIMT was higher with diabetes with the same pattern observed between populations: 0.73 mm, 0.79 mm and 0.82 mm, respectively (P < 0.001). Traditional risk factors (age, male gender, blood pressure and HbA1c) explained 35-45% of the variance of CIMT within each population group. However, differences in CIMT between population groups were maintained after adjustment for these cardiovascular risks plus cholesterol and smoking (P < 0.001). Factor analysis revealed that variables of the metabolic syndrome, together with smoking and elevated C-reactive protein (CRP) and urinary albumin-creatinine ratio (ACR), are likely to explain the higher CIMT in Indigenous Australians (and the urban-remote gradient). Unmeasured variables (genetic, psychosocial and socioeconomic) may also contribute to higher CIMT in these populations. Glycaemic control and metabolic syndrome components contribute significantly to premature atherogenesis in Indigenous Australians and we recommend that therapy should be targeted accordingly.