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.

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

Associations of genetic risk and smoking with incident chronic obstructive pulmonary disease

2021 ◽  
pp. 2101320
Author(s):  
Pei-Dong Zhang ◽  
Xi-Ru Zhang ◽  
Ao Zhang ◽  
Zhi-Hao Li ◽  
Dan Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Risk ◽  
Chronic Obstructive ◽  
Polygenic Risk Score ◽  
Obstructive Pulmonary Disease ◽  
Current Smoking ◽  
High Genetic Risk ◽  
Genome Wide ◽  
Genome Wide Significance

BackgroundGenetic and smoking contribute to chronic obstructive pulmonary disease (COPD), but whether a combined polygenic risk score (PRS) is associated with incident COPD and whether it has a synergistic effect on the smoking remains unclear. We aimed to investigate the association of PRS with COPD and explore whether smoking behaviors could modify such association.MethodsMultivariable Cox proportional models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of the PRS and smoking with COPD.ResultsThe study included 439 255 participants (mean age 56.5; 53.9% female), with a median follow-up of 9.0 years. The PRSlasso containing 2.5 million variants showed better discrimination and a stronger association for incident COPD than the PRS279 containing 279 genome-wide significance variants. Compared with the low genetic risk, the HRs of the medium and high genetic risk were 1.39 (95% CI, 1.31–1.48) and 2.40 (95% CI, 2.24–2.56), respectively. The HR of high genetic risk and current smoking was 11.62 (95% CI, 10.31–13.10) times of low genetic risk and never smoking. There were significant interactions between the PRSlasso and smoking status for incident COPD (p for interaction<0.001). From low genetic risk to high genetic risk, the HRs of current smoking increased from 4.32 (95% CI, 3.69–5.06) to 6.89 (95% CI, 6.21–7.64), and the population-attributable risks of smoking increased from 42.7% to 61.1%.ConclusionPRS constructed from millions of variants below genome-wide significance showed significant associations with incident COPD. Participants with a high genetic risk may be more susceptible to developing COPD when exposed to smoking.

scholarly journals Using polygenic risk score approaches to investigate the common-variant genetic architecture of schizophrenia

2019 ◽  
pp. 8-11
Author(s):  
V. Escott-Price
Keyword(s):  
Risk Score ◽  
Polygenic Risk Score ◽  
Association Analyses ◽  
Polygenic Risk ◽  
Risk Alleles ◽  
The Common ◽  
Professional Occupation ◽  
The Uk ◽  
Genetic Loading ◽  
The Relationship

Is this paper we present a summary of our association analyses of schizophrenia polygenic risk score with a number of phenotypes in a large cohort of people from the UK population (N=442,192). We show that individuals with higher genetic loading to schizophrenia who have not been diagnosed with neurodevelopmental disorders are likely to have some cognitive deficits. Although these deficits may be subtle, they can result in significant effects on educational attainment and professional occupation. We also show that the relationship between schizophrenia liability and fecundity is consistent with sexual selection, with liability in unaffected people being associated with a net increase in fecundity, thereby supporting the persistence of schizophrenia risk alleles.

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 Inclusion of Variants Discovered from Diverse Populations Improves Polygenic Risk Score Transferability

2020 ◽  
Author(s):  
Taylor B. Cavazos ◽  
John S. Witte
Keyword(s):  
Genetic Risk ◽  
African Ancestry ◽  
European Ancestry ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genetic Risk Prediction ◽  
Causal Variants ◽  
The Uk ◽  
The Relationship

ABSTRACTThe majority of polygenic risk scores (PRS) have been developed and optimized in individuals of European ancestry and may have limited generalizability across other ancestral populations. Understanding aspects of PRS that contribute to this issue and determining solutions is complicated by disease-specific genetic architecture and limited knowledge of sharing of causal variants and effect sizes across populations. Motivated by these challenges, we undertook a simulation study to assess the relationship between ancestry and the potential bias in PRS developed in European ancestry populations. Our simulations show that the magnitude of this bias increases with increasing divergence from European ancestry, and this is attributed to population differences in linkage disequilibrium and allele frequencies of European discovered variants, likely as a result of genetic drift. Importantly, we find that including into the PRS variants discovered in African ancestry individuals has the potential to achieve unbiased estimates of genetic risk across global populations and admixed individuals. We confirm our simulation findings in an analysis of HbA1c, asthma, and prostate cancer in the UK Biobank. Given the demonstrated improvement in PRS prediction accuracy, recruiting larger diverse cohorts will be crucial—and potentially even necessary—for enabling accurate and equitable genetic risk prediction across populations.

scholarly journals Polygenic Risk Score Prediction for Endometriosis

2021 ◽  
Vol 3 ◽  
Author(s):  
Kirstine Kloeve-Mogensen ◽  
Palle Duun Rohde ◽  
Simone Twisttmann ◽  
Marianne Nygaard ◽  
Kristina Magaard Koldby ◽  
...  
Keyword(s):  
Risk Score ◽  
Genome Wide Association Study ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Standard Deviation Increase ◽  
Polygenic Risk ◽  
Clinical Risk ◽  
Risk Variants ◽  
Increased Risk ◽  
The Uk

Endometriosis is a major health care challenge because many young women with endometriosis go undetected for an extended period, which may lead to pain sensitization. Clinical tools to better identify candidates for laparoscopy-guided diagnosis are urgently needed. Since endometriosis has a strong genetic component, there is a growing interest in using genetics as part of the clinical risk assessment. The aim of this work was to investigate the discriminative ability of a polygenic risk score (PRS) for endometriosis using three different cohorts: surgically confirmed cases from the Western Danish endometriosis referral Center (249 cases, 348 controls), cases identified from the Danish Twin Registry (DTR) based on ICD-10 codes from the National Patient Registry (140 cases, 316 controls), and replication analysis in the UK Biobank (2,967 cases, 256,222 controls). Patients with adenomyosis from the DTR (25 cases) and from the UK Biobank (1,883 cases) were included for comparison. The PRS was derived from 14 genetic variants identified in a published genome-wide association study with more than 17,000 cases. The PRS was associated with endometriosis in surgically confirmed cases [odds ratio (OR) = 1.59, p = 2.57× 10−7] and in cases from the DTR biobank (OR = 1.50, p = 0.0001). Combining the two Danish cohorts, each standard deviation increase in PRS was associated with endometriosis (OR = 1.57, p = 2.5× 10−11), as well as the major subtypes of endometriosis; ovarian (OR = 1.72, p = 6.7× 10−5), infiltrating (OR = 1.66, p = 2.7× 10−9), and peritoneal (OR = 1.51, p = 2.6 × 10−3). These findings were replicated in the UK Biobank with a much larger sample size (OR = 1.28, p &lt; 2.2× 10−16). The PRS was not associated with adenomyosis, suggesting that adenomyosis is not driven by the same genetic risk variants as endometriosis. Our results suggest that a PRS captures an increased risk of all types of endometriosis rather than an increased risk for endometriosis in specific locations. Although the discriminative accuracy is not yet sufficient as a stand-alone clinical utility, our data demonstrate that genetics risk variants in form of a simple PRS may add significant new discriminatory value. We suggest that an endometriosis PRS in combination with classical clinical risk factors and symptoms could be an important step in developing an urgently needed endometriosis risk stratification tool.

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.

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