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Melissa C Southey

Publications and source records attributed to Melissa C Southey.

3 recordsLinked to original sources
PubMed2026

Baseline Computed Tomography Coronary Angiography and Polygenic Risk Profiles in Adults With Type 2 Diabetes: A Cross-Sectional Analysis From the VOLTAIRE Study.

AIMS: To characterise baseline clinical, anatomical, and genetic cardiovascular risk profiles in participants enrolled in the VOLTAIRE (Evaluation of Polygenic Scores and CT Imaging in Risk Factor Modification in Patients with Type 2 Diabetes) study and examine concordance across these domains. METHODS: This analysis included adults with T2D who completed baseline computed tomography coronary angiography (CTCA) and polygenic risk score (PRS) assessment prior to randomisation in the VOLTAIRE study. Coronary atherosclerosis was evaluated using coronary artery calcium (CAC) score and CTCA-derived stenosis severity. Clinical risk was assessed using the New Zealand Society for the Study of Diabetes 5-year cardiovascular risk calculator. Polygenic risk for coronary artery disease was assessed using a genome-wide PRS and categorised into tertiles. RESULTS: Among 126 participants with T2D (mean age 57.5 ± 8.7 years; 62.7% male), coronary atherosclerotic burden was highly heterogeneous: 34.9% had CAC = 0, whereas 19.8% had CAC ≥ 400. Moderate-to-severe coronary stenosis (≥ 50%) was present in 40.5% of participants overall, including 20.4% of those classified as low clinical risk. PRS distribution was variable (low 37.3%, intermediate 35.7%, high 27.0%). Overlap between anatomical, genetic, and clinical domains was limited, with only 8.7% of participants classified as high risk across all three. CONCLUSIONS: Substantial heterogeneity and limited overlap exist between anatomical, genetic, and clinical cardiovascular risk measures in T2D. These findings support a multimodal approach to risk assessment integrating imaging and genetic profiling. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov; ID: NCT07091162.

Aged↗
PubMed2026

Epigenome-wide analysis of DNA-methylation signatures following climate-related disasters.

BACKGROUND: Floods and tropical cyclones (TCs), two of the most frequent and costliest climate-related disasters worldwide, have been linked to sustained health risks extending beyond acute hazards. However, evidence on the underlying epigenetic mechanisms remains scarce. We aimed to characterize DNA methylation patterns associated with exposure to floods and TCs of varying intensities. METHODS: We collected peripheral blood samples from 479 women (132 twin pairs and 215 of their sisters) across Australia. Blood-derived DNA methylation profiles were assessed using the Illumina HumanMethylation450 BeadChip array. Daily flood and TC exposure data for the 6&#xa0;years preceding each blood draw were obtained from the Dartmouth Flood Observatory and the International Best Track Archive for Climate Stewardship, respectively, and linked to participants based on residential addresses. Using a within-sibship analytical framework that accounted for shared familial factors and other relevant covariates, we examined associations between flood and TC exposures of varying intensities and site-specific methylation at each cytosine-guanine dinucleotide (CpG). Differentially methylated regions (DMRs) were identified using a combination of the comb-p and DMRcate algorithms. RESULTS: There were 164 CpGs and 219 DMRs associated with flood and TC exposures (Bonferroni-adjusted p value&#x2009;<&#x2009;0.05), mapping to 242 genes enriched in pathways related to inflammation and immune regulation. These genes have been implicated in a wide range of human diseases or phenotypes. The number of differentially methylated CpGs increased with more recent and higher-intensity exposures. Intensity-dependent gene regulation was observed, with genes such as AMT and C22orf45 consistently implicated across various exposure levels, whereas RNF39 and ACY3 emerged only at higher intensities. CONCLUSIONS: Exposures to floods and TCs were associated with differentially DNA methylated signals across the human genome, exhibiting intensity-dependent patterns. The identified signals and related gene pathways may shed light on the biological mechanism underlying the profound health effects of climate-related disasters.

Humans↗
PubMed2026

Risks of non-breast, non-ovarian cancers for BRCA1 and BRCA2&#xa0;pathogenic variant carriers: a prospective cohort study.

BACKGROUND: The non-breast non-ovarian cancers associated with BRCA1 and BRCA2 pathogenic variants (PVs) are controversial. We aimed to examine this using a prospective cohort&#xa0;design. METHODS: This study included 1260 BRCA1 and 1058 BRCA2 PV carriers (91% were females) from two consortia: the Breast Cancer Family Registry (BCFR) and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer Follow-Up Study (kConFab-FUS). The carriers were free of cancer other than breast or ovarian cancer&#xa0;at baseline and had a median baseline age of 45.5&#xa0;years. For 16 types of non-breast, non-ovarian cancers, standardized incidence ratios (SIRs) relative to population incidence, the probabilities of relative risk effect size&#x2009;>&#x2009;2 (i.e., moderate risk) and cumulative risks to age 80&#xa0;years were estimated. RESULTS: During a median follow-up time of 11.4&#xa0;years, 161 non-breast, non-ovarian cancers were observed. For BRCA1 PV carriers, little evidence of increased risk was observed. The prostate, pancreatic, and all non-pancreatic cancer SIRs were 1.7 (95% CI 0.7-4.2), 1.1 (95% CI 0.3-4.6) and 0.85 (95% CI 0.68-1.06), respectively; the probabilities of relative risk&#x2009;>&#x2009;2 were 0 and 67% for prostate and pancreatic cancers, respectively. For BRCA2 PV carriers, increased risks of pancreatic (SIR&#x2009;=&#x2009;6.6, 95% CI 3.8-11.6), prostate (SIR&#x2009;=&#x2009;3.6, 95% CI 1.9-6.8) and stomach (SIR&#x2009;=&#x2009;3.1, 95% CI 1.01-9.8) cancer were observed, with a cumulative risk to age 80&#xa0;years of 8.3, 82.0, and 1.6%, respectively. For all the other non-breast, non-ovarian cancers combined, the SIR was 0.85 (95% CI 0.66-1.10). CONCLUSIONS: Apart from pancreatic, prostate, and possibly stomach cancers for BRCA2 PV carriers, and possibly pancreatic cancer for BRCA1 PV carriers, there is no evidence that BRCA1 and BRCA2 PV carriers have substantially increased risks of other non-breast, non-ovarian cancers. Our prospective risk estimates are informative for cancer risk assessment for people with BRCA1 and BRCA2 PVs.

Humans↗