scholarly journals Parental lifespan and polygenic risk score of longevity are associated with white matter hyperintensities

2021 ◽  
Author(s):  
Chao Dong ◽  
Anbupalam Thalamuthu ◽  
Jiyang Jiang ◽  
Karen A. Mather ◽  
Henry Brodaty ◽  
...  
Keyword(s):  
White Matter ◽  
Risk Score ◽  
White Matter Hyperintensity ◽  
Human Longevity ◽  
Cerebral White Matter ◽  
Polygenic Risk Score ◽  
Replication Sample ◽  
Polygenic Risk ◽  
Discovery Sample ◽  
Brain Ageing

AbstractHuman longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain ageing. In this study, we investigated the associations of parental lifespan (parental age at death) and polygenic risk score for longevity (longevity-PRS) with structural magnetic resource imaging (MRI) brain metrics considered to reflect the brain ageing process. We used a discovery sample (N = 19136) from the UK Biobank and a replication sample (N =809) from the Sydney Memory and Ageing Study and the Older Australian Twins Study. We found lower cerebral white matter hyperintensity (WMH) volumes to be significantly associated with longer parental lifespan in the discovery and replication samples and higher longevity-PRS in the discovery sample and a similar trend in the replication sample. The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus. Additionally, the effects of longevity-PRS on the association were more prominent in males, especially in the older-male group. Our findings suggest that human longevity-related genes may have an influence on WMH burden, suggesting WMH volume may be a biomarker for longevity and an ageing endophenotype.

scholarly journals Genome-Wide Genotyping Demonstrates a Polygenic Risk Score Associated With White Matter Hyperintensity Volume in CADASIL

Stroke ◽  
2014 ◽  
Vol 45 (4) ◽  
pp. 968-972 ◽  
Author(s):  
Christian Opherk ◽  
Mariya Gonik ◽  
Marco Duering ◽  
Rainer Malik ◽  
Eric Jouvent ◽  
...  
Keyword(s):  
White Matter ◽  
Risk Score ◽  
White Matter Hyperintensity ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide

scholarly journals Schizophrenia polygenic risk score influence on white matter microstructure

2020 ◽  
Vol 121 ◽  
pp. 62-67 ◽  
Author(s):  
Beatriz Simões ◽  
Evangelos Vassos ◽  
Sukhi Shergill ◽  
Colm McDonald ◽  
Timothea Toulopoulou ◽  
...  
Keyword(s):  
White Matter ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
White Matter Microstructure

1645-P: Polygenic Risk Score for Prediction of Complications in Men and Women with Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1645-P
Author(s):  
JOHANNE TREMBLAY ◽  
REDHA ATTAOUA ◽  
MOUNSIF HALOUI ◽  
RAMZAN TAHIR ◽  
CAROLE LONG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Men And Women ◽  
Polygenic Risk ◽  
Prediction Of Complications

304-OR: Polygenic Risk Score Predicts Type 2 Diabetes Susceptibility in a Diverse Consumer Genetic Database

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 304-OR
Author(s):  
MICHAEL L. MULTHAUP ◽  
RYOSUKE KITA ◽  
NICHOLAS ERIKSSON ◽  
STELLA ASLIBEKYAN ◽  
JANIE SHELTON ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Diabetes Susceptibility ◽  
Genetic Database ◽  
Polygenic Risk

P4-240: Using polygenic risk score to predict Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_19) ◽  
pp. P872-P872 ◽  
Author(s):  
Valentina Escott-Price ◽  
Rebecca Sims ◽  
Denise Harold ◽  
Maria Vronskaya ◽  
Peter Holmans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals Relative contributions of family history and a polygenic risk score on COPD and related outcomes: COPDGene and ECLIPSE studies

2020 ◽  
Vol 7 (1) ◽  
pp. e000755
Author(s):  
Matthew Moll ◽  
Sharon M. Lutz ◽  
Auyon J. Ghosh ◽  
Phuwanat Sakornsakolpat ◽  
Craig P. Hersh ◽  
...  
Keyword(s):  
Family History ◽  
Risk Score ◽  
Characteristic Curve ◽  
Significant Proportion ◽  
Chronic Obstructive ◽  
Polygenic Risk Score ◽  
Positive Interaction ◽  
Polygenic Risk ◽  
Mediation Analyses ◽  
The Impact

IntroductionFamily history is a risk factor for chronic obstructive pulmonary disease (COPD). We previously developed a COPD risk score from genome-wide genetic markers (Polygenic Risk Score, PRS). Whether the PRS and family history provide complementary or redundant information for predicting COPD and related outcomes is unknown.MethodsWe assessed the predictive capacity of family history and PRS on COPD and COPD-related outcomes in non-Hispanic white (NHW) and African American (AA) subjects from COPDGene and ECLIPSE studies. We also performed interaction and mediation analyses.ResultsIn COPDGene, family history and PRS were significantly associated with COPD in a single model (PFamHx <0.0001; PPRS<0.0001). Similar trends were seen in ECLIPSE. The area under the receiver operator characteristic curve for a model containing family history and PRS was significantly higher than a model with PRS (p=0.00035) in NHWs and a model with family history (p<0.0001) alone in NHWs and AAs. Both family history and PRS were significantly associated with measures of quantitative emphysema and airway thickness. There was a weakly positive interaction between family history and the PRS under the additive, but not multiplicative scale in NHWs (relative excess risk due to interaction=0.48, p=0.04). Mediation analyses found that a significant proportion of the effect of family history on COPD was mediated through PRS in NHWs (16.5%, 95% CI 9.4% to 24.3%), but not AAs.ConclusionFamily history and the PRS provide complementary information for predicting COPD and related outcomes. Future studies can address the impact of obtaining both measures in clinical practice.

scholarly journals Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans

Leukemia ◽  
2021 ◽  
Author(s):  
Geffen Kleinstern ◽  
J. Brice Weinberg ◽  
Sameer A. Parikh ◽  
Esteban Braggio ◽  
Sara J. Achenbach ◽  
...  
Keyword(s):  
Environmental Factors ◽  
B Cell ◽  
Risk Score ◽  
Genetic Factors ◽  
Strong Predictor ◽  
Lymphocytic Leukemia ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
C Statistic

AbstractMonoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-susceptibility variants has been found to be associated with CLL risk among individuals of European-ancestry(EA). Here, we evaluate these variants, the PRS, and environmental factors for MBL risk. We also evaluate these variants and the CLL-PRS among African-American (AA) and EA-CLL cases and controls. Our study included 560 EA MBLs, 869 CLLs (696 EA/173 AA), and 2866 controls (2631 EA/235 AA). We used logistic regression, adjusting for age and sex, to estimate odds ratios (OR) and 95% confidence intervals within each race. We found significant associations with MBL risk among 21 of 41 variants and with the CLL-PRS (OR = 1.86, P = 1.9 × 10−29, c-statistic = 0.72). Little evidence of any association between MBL risk and environmental factors was observed. We observed significant associations of the CLL-PRS with EA-CLL risk (OR = 2.53, P = 4.0 × 10−63, c-statistic = 0.77) and AA-CLL risk (OR = 1.76, P = 5.1 × 10−5, c-statistic = 0.62). Inherited genetic factors and not environmental are associated with MBL risk. In particular, the CLL-PRS is a strong predictor for both risk of MBL and EA-CLL, but less so for AA-CLL supporting the need for further work in this population.

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