Effects of genetic risk for alcohol dependence and onset of regular drinking on the progression to alcohol dependence: A polygenic risk score approach

2021 ◽  
pp. 109117
Author(s):  
Ellen W. Yeung ◽  
Kellyn M. Spychala ◽  
Alex P. Miller ◽  
Jacqueline M. Otto ◽  
Joseph D. Deak ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Risk Score ◽  
Genetic Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals Diet quality indices, genetic risk and risk of cardiovascular disease and mortality: a longitudinal analysis of 77 004 UK Biobank participants

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e045362
Author(s):  
Katherine M Livingstone ◽  
Gavin Abbott ◽  
Steven J Bowe ◽  
Joey Ward ◽  
Catherine Milte ◽  
...  
Keyword(s):  
Risk Score ◽  
Diet Quality ◽  
Genetic Risk ◽  
Lower Risk ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Quality Indices ◽  
Polygenic Risk ◽  
All Cause Mortality ◽  
Cvd Mortality

ObjectivesTo examine associations of three diet quality indices and a polygenic risk score with incidence of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke.DesignProspective cohort study.SettingUK Biobank, UK.Participants77 004 men and women (40–70 years) recruited between 2006 and 2010.Main outcome measuresA polygenic risk score was created from 300 single nucleotide polymorphisms associated with CVD. Cox proportional HRs were used to estimate independent effects of diet quality and genetic risk on all-cause mortality, CVD mortality, MI and stroke risk. Dietary intake (Oxford WebQ) was used to calculate Recommended Food Score (RFS), Healthy Diet Indicator (HDI) and Mediterranean Diet Score (MDS).ResultsNew all-cause (n=2409) and CVD (n=364) deaths and MI (n=1141) and stroke (n=748) events were identified during mean follow-ups of 7.9 and 7.8 years, respectively. The adjusted HR associated with one-point higher RFS for all-cause mortality was 0.96 (95% CI: 0.94 to 0.98), CVD mortality was 0.94 (95% CI: 0.90 to 0.98), MI was 0.97 (95% CI: 0.95 to 1.00) and stroke was 0.94 (95% CI: 0.91 to 0.98). The adjusted HR for all-cause mortality associated with one-point higher HDI and MDS was 0.97 (95% CI: 0.93 to 0.99) and 0.95 (95% CI: 0.91 to 0.98), respectively. The adjusted HR associated with one-point higher MDS for stroke was 0.93 (95% CI: 0.87 to 1.00). There was little evidence of associations between HDI and risk of CVD mortality, MI or stroke. There was evidence of an interaction between diet quality and genetic risk score for MI.ConclusionHigher diet quality predicted lower risk of all-cause mortality, independent of genetic risk. Higher RFS was also associated with lower risk of CVD mortality and MI. These findings demonstrate the benefit of following a healthy diet, regardless of genetic risk.

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

2018 ◽  
Vol 42 (3) ◽  
pp. 520-530 ◽  
Author(s):  
Jeanne E. Savage ◽  
Jessica E. Salvatore ◽  
Fazil Aliev ◽  
Alexis C. Edwards ◽  
Matthew Hickman ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Risk Score ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals Capturing additional genetic risk from family history for improved polygenic risk prediction

2022 ◽  
Author(s):  
Tianyuan Lu ◽  
Vincenzo Forgetta ◽  
J Brent Richards ◽  
Celia MT Greenwood
Keyword(s):  
Family History ◽  
Risk Prediction ◽  
Risk Score ◽  
Genetic Risk ◽  
Adult Height ◽  
Prediction Models ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Parental History ◽  
Polygenic Risk

Family history of complex traits may reflect transmitted rare pathogenic variants, intrafamilial shared exposures to environmental and lifestyle factors, as well as a common genetic predisposition. We developed a latent factor model to quantify trait heritability in excess of that captured by a common variant-based polygenic risk score, but inferable from family history. We applied our model to predict adult height for 941 children in the Avon Longitudinal Study of Parents and Children cohort as well as 11 complex diseases for ~400,000 European ancestry participants in the UK Biobank. Parental history brought consistent significant improvements in the predictive power of polygenic risk prediction. For instance, a joint predictor was able to explain ~55% of the total variance in sex-adjusted adult height z-scores, close to the estimated heritability. Our work showcases an innovative paradigm for risk calculation, and supports incorporation of family history into polygenic risk score-based genetic risk prediction models.

The BARCODE1 pilot study targeting men with increased genetic risk of developing prostate cancer: Examining the feasibility of a community-based screening program using polygenic risk score to target screening.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 227-227
Author(s):  
Jana Kathlyn McHugh ◽  
Sarah Benafif ◽  
Holly ni Raghallaigh ◽  
Elizabeth Bancroft ◽  
Zsofia Kote-Jarai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Primary Care ◽  
Dna Extraction ◽  
Risk Score ◽  
Genetic Risk ◽  
Population Screening ◽  
Low Risk ◽  
Polygenic Risk Score ◽  
Genetic Profiling ◽  
Polygenic Risk

227 Background: A significant proportion of Prostate cancer (PrCa) risk is attributable to heritable risk factors of which only a minority are high risk Mendelian traits. A greater proportion of PrCa is due to the combined effect of multiple low risk variants. There have been approximately 170 single nucleotide polymorphisms (SNPs) identified that are associated with PrCa risk in Europeans. Although each of these confer a low to moderate risk of PrCa, the cumulative risk (polygenic risk score, PRS) of increasing numbers of these risk alleles may confer a substantial relative risk. In PrCa genetic profiling, using PRS, could be used to target population screening to those at highest risk. BARCODE1 is the first study to prospectively review the use of a genetic profile in PrCa screening in the general population in the UK. Methods: Our study invited healthy males aged 55-69 to participate through their Primary Care physicians. Collection kits were mailed to retrieve saliva samples. Genotyping was carried out after DNA extraction using a study specific assay and the PRS was calculated for each participant using the sum of weighted alleles for 130 risk loci. Prostate MRI and Biopsy were then offered to men in the top 10% of the genetic risk profile. Results: 1434 men were invited by letter to participate. The uptake was 26%, of whom 87% of men were eligible for inclusion. Following DNA extraction, genotyping, and quality control checks, data were available for 297 men. 25 participants had PRS in the top 10% and were invited for screening; 19 underwent a prostate MRI, and 18 went on to have a systematic (+/- targeted prostate biopsy. There were 7 diagnoses of PrCa (38.9%). The cancers detected were low-risk and are being managed with Active Surveillance (AS). Results of the first year of follow up will be presented and an update of the main study which aims to recruit 5000 men. Conclusions: The BARCODE1 pilot has shown the feasibility of this population-based study, with an overall uptake of 26% and a cancer incidence of nearly 40%. We have identified approximately 70 Primary care providers who have contributed to the transition to the full BARCODE1 study, which will aim to recruit 5,000 men. The BARCODE1 study results will be important in defining the role of PRS genetic profiling in targeted PrCa population screening. Clinical trial information: IRAS257684.

T61SUICIDE DEATHS SELECTED FOR GENETIC RISK: POLYGENIC RISK SCORE CHARACTERISTICS AND HIGH-IMPACT SEQUENCE VARIANTS

2019 ◽  
Vol 29 ◽  
pp. S248
Author(s):  
Hilary Coon ◽  
Andrey Shabalin ◽  
Emily DiBlasi ◽  
Brooks Keeshin ◽  
Amanda Bakian ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
High Impact ◽  
Polygenic Risk Score ◽  
Sequence Variants ◽  
Polygenic Risk

scholarly journals Polygenic risk score, healthy lifestyles, and risk of incident depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhi Cao ◽  
Hongxi Yang ◽  
Yixuan Ye ◽  
Yuan Zhang ◽  
Shu Li ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Lifestyle Factors ◽  
Polygenic Risk Score ◽  
Healthy Lifestyles ◽  
Current Smoking ◽  
Polygenic Risk ◽  
High Genetic Risk ◽  
Moderate Alcohol Intake ◽  
The Uk

AbstractGenetic factors increase the risk of depression, but the extent to which this can be offset by modifiable lifestyle factors is unknown. We investigated whether a combination of healthy lifestyles is associated with lower risk of depression regardless of genetic risk. Data were obtained from the UK Biobank and consisted of 339,767 participants (37–73 years old) without depression between 2006 and 2010. Genetic risk was categorized as low, intermediate, or high according to polygenic risk score for depression. A combination of healthy lifestyles factors—including no current smoking, regular physical activity, a healthy diet, moderate alcohol intake and a body mass index <30 kg/m2—was categorized into favorable, intermediate, and unfavorable lifestyles. The risk of depression was 22% higher among those at high genetic risk compared with those at low genetic risk (HR = 1.22, 95% CI: 1.14–1.30). Participants with high genetic risk and unfavorable lifestyle had a more than two-fold risk of incident depression compared with low genetic risk and favorable lifestyle (HR = 2.18, 95% CI: 1.84–2.58). There was no significant interaction between genetic risk and lifestyle factors (P for interaction = 0.69). Among participants at high genetic risk, a favorable lifestyle was associated with nearly 50% lower relative risk of depression than an unfavorable lifestyle (HR = 0.51, 95% CI: 0.43–0.60). We concluded that genetic and lifestyle factors were independently associated with risk of incident depression. Adherence to healthy lifestyles may lower the risk of depression regardless of genetic risk.

scholarly journals Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants

BMJ ◽  
2018 ◽  
pp. k4168 ◽  
Author(s):  
Loes CA Rutten-Jacobs ◽  
Susanna C Larsson ◽  
Rainer Malik ◽  
Kristiina Rannikmäe ◽  
Cathie L Sudlow ◽  
...  
Keyword(s):  
Cohort Study ◽  
Risk Score ◽  
Genetic Risk ◽  
Cox Regression ◽  
Healthy Lifestyle ◽  
Lifestyle Factors ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Increased Risk

AbstractObjectiveTo evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.DesignProspective population based cohort study.SettingUK Biobank Study, UK.Participants306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.Main outcome measureHazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was constructed at P<1×10−5to test for an association with incident stroke. Adherence to a healthy lifestyle was determined on the basis of four factors: non-smoker, healthy diet, body mass index <30 kg/m2, and regular physical exercise.ResultsDuring a median follow-up of 7.1 years (2 138 443 person years), 2077 incident strokes (1541 ischaemic stroke, 287 intracerebral haemorrhage, and 249 subarachnoid haemorrhage) were ascertained. The risk of incident stroke was 35% higher among those at high genetic risk (top third of polygenic score) compared with those at low genetic risk (bottom third): hazard ratio 1.35 (95% confidence interval 1.21 to 1.50), P=3.9×10−8. Unfavourable lifestyle (0 or 1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3 or 4 healthy lifestyle factors): 1.66 (1.45 to 1.89), P=1.19×10−13. The association with lifestyle was independent of genetic risk stratums.ConclusionIn this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasise the benefit of entire populations adhering to a healthy lifestyle, independent of genetic risk.

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