Dataset Information

Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals.

ABSTRACT:

Background

Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest.

Methods

We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12 712 individuals in the ASPirin in Reducing Events in the Elderly Trial. We evaluated incident melanomas diagnosed during the trial and prevalent melanomas diagnosed preenrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per SD) and categorical (low-risk [0%-20%], medium-risk [21%-80%], high-risk [81%-100%] groups) with incident melanoma. Logistic regression examined the association between PRS and prevalent melanoma.

Results

At baseline, mean participant age was 75 years; 55.0% were female, and 528 (4.2%) had prevalent melanomas. During follow-up (median = 4.7 years), 120 (1.0%) incident cutaneous melanomas occurred, 98 of which were in participants with no history. PRS was associated with incident melanoma (hazard ratio = 1.46 per SD, 95% confidence interval [CI] = 1.20 to 1.77) and prevalent melanoma (odds ratio [OR] = 1.55 per SD, 95% CI = 1.42 to 1.69). Participants in the highest-risk PRS group had increased risk compared with the low-risk group for incident melanoma (OR = 2.51, 95% CI = 1.28 to 4.92) and prevalent melanoma (OR = 3.66, 95% CI = 2.69 to 5.05). When stratifying by sex, only males had an association between the PRS and incident melanoma, whereas both sexes had an association between the PRS and prevalent melanoma.

Conclusions

A genomic risk score is associated with melanoma risk in older individuals and may contribute to targeted surveillance.

SUBMITTER: Bakshi A

PROVIDER: S-EPMC8921762 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals.

Bakshi Andrew A Yan Mabel M Riaz Moeen M Polekhina Galina G Orchard Suzanne G SG Tiller Jane J Wolfe Rory R Joshi Amit A Cao Yin Y McInerney-Leo Aideen M AM Yanes Tatiane T Janda Monika M Soyer H Peter HP Cust Anne E AE Law Matthew H MH Gibbs Peter P McLean Catriona C Chan Andrew T AT McNeil John J JJ Mar Victoria J VJ Lacaze Paul P

Journal of the National Cancer Institute 20211001 10

<h4>Background</h4>Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest.<h4>Methods</h4>We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12 712 individuals in the ASPirin in Reducing Events in the Elderly Trial ...[more]

PMID: 33837773

Similar Datasets

Project description:BackgroundIntracerebral hemorrhage (ICH) has an estimated heritability of 29%. We developed a genomic risk score for ICH and determined its predictive power in comparison to standard clinical risk factors.MethodsWe combined genome-wide association data from individuals of European ancestry for ICH and related traits in a meta-genomic risk score ([metaGRS]; 2.6 million variants). We tested associations with ICH and its predictive performance in addition to clinical risk factors in a held-out validation dataset (842 cases and 796 controls). We tested associations with risk of incident ICH in the population-based UK Biobank cohort (486 784 individuals, 1526 events, median follow-up 11.3 years).ResultsOne SD increment in the metaGRS was significantly associated with 31% higher odds for ICH (95% CI, 1.16-1.48) in age-, sex- and clinical risk factor-adjusted models. The metaGRS identified individuals with almost 5-fold higher odds for ICH in the top score percentile (odds ratio, 4.83 [95% CI, 1.56-21.2]). Predictive models for ICH incorporating the metaGRS in addition to clinical predictors showed superior performance compared to the clinical risk factors alone (c-index, 0.695 versus 0.686). The metaGRS showed similar associations for lobar and nonlobar ICH, independent of the known APOE risk locus for lobar ICH. In the UK Biobank, the metaGRS was associated with higher risk of incident ICH (hazard ratio, 1.15 [95% CI, 1.09-1.21]). The associations were significant within both a relatively high-risk population of antithrombotic medications users, as well as among a relatively low-risk population with a good control of vascular risk factors and no use of anticoagulants.ConclusionsWe developed and validated a genomic risk score that predicts lifetime risk of ICH beyond established clinical risk factors among individuals of European ancestry. Whether implementation of the score in risk prognostication models for high-risk populations, such as patients under antithrombotic treatment, could improve clinical decision making should be explored in future studies.

Project description:5.8 M living Americans have experienced a stroke at some time in their lives, 780K had either their first or a recurrent stroke this year, and 150K died from strokes this year. Stroke costs about $66B annually in the US, and also results in serious, long-term disability. Therefore, it is prudent to identify all possible risk factors and their effects so that appropriate intervention points may be targeted.Baseline (1993-1994) interview data from the nationally representative Survey on Assets and Health Dynamics among the Oldest Old (AHEAD) were linked to 1993-2005 Medicare claims. Participants were 5,511 self-respondents >or= 70 years old. Two ICD9-CM case-identification approaches were used. Two approaches to stroke case-identification based on ICD9-CM codes were used, one emphasized sensitivity and the other emphasized specificity. Participants were censored at death or enrollment into managed Medicare. Baseline risk factors included sociodemographic, socioeconomic, place of residence, health behavior, disease history, and functional and cognitive status measures. A time-dependent marker reflecting post-baseline non-stroke hospitalizations was included to reflect health shocks, and sensitivity analyses were conducted to identify its peak effect. Competing risk, proportional hazards regression was used.Post-baseline strokes occurred for 545 (9.9%; high sensitivity approach) and 374 (6.8%; high specificity approach) participants. The greatest static risks involved increased age, being widowed or never married, living in multi-story buildings, reporting a baseline history of diabetes, hypertension, or stroke, and reporting difficulty picking up a dime, refusing to answer the delayed word recall test, or having poor cognition. Risks were similar for both case-identification approaches and for recurrent and first-ever vs. only first-ever strokes. The time-dependent health shock (recent hospitalization) marker did not alter the static model effect estimates, but increased stroke risk by 200% or more.The effect of our health shock marker (a time-dependent recent hospitalization indicator) was large and did not mediate the effects of the traditional risk factors. This suggests an especially vulnerable post-hospital transition period from adverse effects associated with both their underlying health shock (the reasons for the recent hospital admission) and the consequences of their treatments.

Project description:BackgroundGlucose metabolic disorder is associated with the risk of heart failure (HF). Adiposity is a comorbidity that is inextricably linked with abnormal glucose metabolism in older individuals. However, the effect of adiposity on the association between glucose metabolic disorder and HF risk, and the underlying mechanism remain unclear.MethodsA total of 13,251 participants aged ≥ 60 years from a cohort study were categorized into euglycemia, prediabetes, uncontrolled diabetes, and well-controlled diabetes. Adiposity was assessed using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Adiposity-associated metabolic activities were evaluated using adiponectin-to-leptin ratio (ALR), homeostatic model assessment of insulin resistance (HOMA-IR), and triglyceride-glucose index (TyG). The first occurrence of HF served as the outcome during the follow-up period.ResultsA total of 1,138 participants developed HF over the course of an average follow-up period of 10.9 years. The rate of incident HF occurrence was higher in prediabetes, uncontrolled diabetes, and well-controlled diabetes participants compared to that in euglycemia participants. However, the high rates were significantly attenuated by BMI, VFA, and WHR. For WHR in particular, the hazard ratio for incident HF was 1.18 (95% confidence interval (CI): 1.03, 1.35, Padj.=0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, Padj.<0.001) in uncontrolled diabetes, and 1.10 (95% CI: 0.85, 1.43, Padj.=0.466) in well-controlled diabetes. The population attributable risk percentage for central obesity classified by WHR for incident HF was 30.3% in euglycemia, 50.0% in prediabetes, 48.5% in uncontrolled diabetes, and 54.4% in well-controlled diabetes. Adiposity measures, especially WHR, showed a significant interaction with glucose metabolic disorder in incident HF (all Padj.<0.001). ALR was negatively associated and HOMA-IR and TyG were positively associated with BMI, WHR, VFA, and incident HF (all Padj.<0.05). ALR, HOMA-IR, and TyG mediated the associations for BMI, WHR and VFA with incident HF (all Padj.<0.05).ConclusionsAdiposity attenuated the association of glucose metabolic disorder with incident HF. The results also showed that WHR may be an appropriate indicator for evaluating adiposity in older individuals. Adiposity-associated metabolic activities may have a bridging role in the process of adiposity attenuating the association between glucose metabolic disorder and incident HF.Trial registrationretrospectively registered number: ChiCTR-EOC-17,013,598.

Dataset Information

Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals.

Background

Methods

Results

Conclusions

Publications

Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets