Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples

Abstract Hereditary factors have a strong influence on prostate cancer (PC) risk and poorer outcomes, thus stratification by genetic factors addresses a critical need for targeted PC screening and risk-adapted follow-up. In this Finnish population-based retrospective study 2283 clinically diagnosed and 455 screen-detected patients from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC), 2400 healthy individuals have been involved. Individual genetic risk through establishment of a polygenic risk score based on 55 PC risk SNPs identified through the Finnish subset of the Collaborative Oncological Gene-Environment Study was assessed. Men with PC had significantly higher median polygenic risk score compared to the controls (6.59 vs. 3.83, P < 0.0001). The polygenic risk score above the control median was a significant predictor of PC (OR 2.13, 95% CI 1.90–2.39). The polygenic risk score predicted the risk of PC with an AUC of 0.618 (95% CI 0.60–0.63). Men in the highest polygenic risk score quartile were 2.8—fold (95% CI 2.4–3.30) more likely to develop PC compared with men in the lowest quartile. In the FinRSPC cohort, a significantly higher percentage of men had a PSA level of ≥ 4 ng/mL in polygenic risk score quartile four compared to quartile one (18.7% vs 8.3%, P < 0.00001). Adding the PRS to a PSA-only model contributed additional information in predicting PC in the FinRSPC model. Results strongly suggest that use of the polygenic risk score would facilitate the identification of men at increased risk for PC.

Download Full-text

Association of the polygenic risk score for schizophrenia with mortality and suicidal behavior - A Danish population-based study

Schizophrenia Research ◽

10.1016/j.schres.2016.12.001 ◽

2017 ◽

Vol 184 ◽

pp. 122-127 ◽

Cited By ~ 12

Author(s):

Thomas M. Laursen ◽

Betina B. Trabjerg ◽

Ole Mors ◽

Anders D. Børglum ◽

David M. Hougaard ◽

...

Keyword(s):

Risk Score ◽

Suicidal Behavior ◽

Population Based ◽

Polygenic Risk Score ◽

Danish Population ◽

Population Based Study ◽

Polygenic Risk

Download Full-text

Association of the Polygenic Risk Score With the Probability of Prodromal Parkinson’s Disease in Older Adults

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.739571 ◽

2021 ◽

Vol 14 ◽

Author(s):

Maria I. Maraki ◽

Alexandros Hatzimanolis ◽

Niki Mourtzi ◽

Leonidas Stefanis ◽

Mary Yannakoulia ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Risk Score ◽

Strong Relationship ◽

Population Based ◽

Community Dwelling ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Common Genetic Variants ◽

Research Criteria

Several studies have investigated the association of the Parkinson’s disease (PD) polygenic risk score (PRS) with several aspects of well-established PD. We sought to evaluate the association of PRS with the prodromal stage of PD. We calculated PRS in a longitudinal sample (n = 1120) of community dwelling individuals ≥ 65 years from the HELIAD (The Hellenic Longitudinal Investigation of Aging and Diet) study in order to evaluate the association of this score with the probability of prodromal PD or any of the established risk and prodromal markers in MDS research criteria, using regression multi-adjusted models. Increases in PRS estimated from GWAS summary statistics’ ninety top SNPS with p < 5 × 10–8 was associated with increased odds of having probable/possible prodromal PD (i.e., ≥ 30% probability, OR = 1.033, 95%CI: 1.009–1.057 p = 0.006). From the prodromal PD risk markers, significant association was found between PRS and global cognitive deficit exclusively (p = 0.003). To our knowledge, our study is the first population based study investigating the association between PRS scores and prodromal markers of Parkinson’s disease. Our results suggest a strong relationship between the accumulation of many common genetic variants, as measured by PRS, and cognitive deficits.

Download Full-text