Metabolomic Profiles Associated With Incident Ischemic Stroke

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013129
Author(s):  
Raji Balasubramanian ◽  
Jie Hu ◽  
Marta Guasch-Ferre ◽  
Jun Li ◽  
Farzaneh Sorond ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Risk Prediction ◽  
Methionine Sulfoxide ◽  
Health Study ◽  
Plasma Metabolites ◽  
Q Value ◽  
Logistic Regression Models ◽  
Increased Risk ◽  
Traditional Risk Factors

Background:Women have higher lifetime risk of stroke than men, and metabolic factors seem more strongly associated with stroke for women than men. However, few studies in either men or women have evaluated metabolomic profiles and incident stroke.Methods:We applied liquid chromatography-tandem mass spectrometry to measure 519 plasma metabolites in a discovery set of women in the Nurses’ Health Study ([NHS], 454 incident ischemic stroke cases, 454 controls) with validation in two independent, prospective cohorts: Prevención con Dieta Mediterránea ([PREDIMED], 118 stroke cases, 791 controls), and Nurses’ Health Study 2 ([NHS2], 49 ischemic stroke cases, 49 controls). We applied logistic regression models with stroke as the outcome to adjust for multiple risk factors; the false discovery rate (FDR) was controlled through the q value method.Results:Twenty-three metabolites were significantly associated with incident stroke in NHS after adjustment for traditional risk factors (q value <0.05). Of these, 14 metabolites were available in PREDIMED and 3 were significantly associated with incident stroke: methionine sulfoxide, N6-acetyllysine, and sucrose (q value<0.05). In NHS2, one of the 23 metabolites (glucuronate) was significantly associated with incident stroke (q value <0.05). For all four metabolites, higher levels were associated with increased risk. These four metabolites were used to create a stroke metabolite score (SMS) in the NHS and tested in PREDIMED. Per unit of standard deviation of SMS, the odds ratio for incident stroke was 4.12 (95% CI: 2.26 – 7.51) in PREDIMED, after adjustment for risk factors. In PREDIMED, the area under the ROC curve (AUC) for the model including SMS and traditional risk factors was 0.70 (95% CI: 0.75-0.79) versus the AUC for the model including the traditional risk factors only of 0.65 (95% CI: 0.70-75), corresponding to a 5% improvement in risk prediction with SMS (p < 0.005).Discussion:Metabolites associated with stroke included two amino acids, a carboxylic acid and sucrose. A composite SMS including these metabolites was associated with ischemic stroke and showed improvement in risk prediction beyond traditional risk factors.Classification of Evidence:This study provides Class II evidence that a stroke metabolic score accurately predicts incident ischemic stroke risk.

Abstract 19: Dietary Lipophilic Load and Dietary Lipophilic Index with Risk of Coronary Heart Disease in Middle-Aged Women: Beyond Conventional Fat Classifications

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Eric L Ding ◽  
Katerina M De Vito ◽  
Hongyu Wu ◽  
Qi Sun ◽  
An Pan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Dietary Fat ◽  
Hdl Cholesterol ◽  
Health Study ◽  
Chd Risk ◽  
Increased Risk ◽  
Total Fat ◽  
Traditional Risk Factors

Introduction: Studies indicate dietary types of fats are associated with risk of coronary heart disease (CHD). Traditional broad classifications may incompletely capture the diversity of fatty acids on CHD. The novel lipid index Dietary Lipophilic Load (DLL) reflects a unique combination of fatty acid fluidity, intermolecular attraction, plus relative fat quantity, while Dietary Lipophilic Index (DLI) is a measure of average fat fluidity, regardless of fat quantity. Thus, we evaluated the association, DLL and DLI, with risk of incident CHD. METHODS: Participants included 30,932 women in the Women’s Health Study (WHS), who were free of major chronic diseases at baseline. DLL was calculated by weighted summation of the multiplicative product of each fatty acid’s intakes (g/day) and its melting points (Celcius); DLI was calculated by dividing DLL by total fat intake (g/day). Hazard ratios (HRs) were adjusted for established risk factors, with updated dietary data, and potential mediators. We also investigated hypothesized interactions with C-Reactive Protein (CRP). RESULTS: There were 1137 cases of incident CHD in 525,828 person-years over 19 years follow-up. At baseline in over 27,000 women with blood samples, DLL and DLI were not correlated with serum cholesterol, triglyceride, HbA1c, ICAM-1, or CRP biomarkers (r<0.02 for all). In overall multivariate analysis, DLL was associated with higher risk of CHD (extreme quintile HR=1.40, 95%CI: 1.11-1.76, P trend=0.0002), while DLI was not (HR=0.83, 95%CI: 0.67-1.03, P trend=0.75). DLL results were independent beyond adjustment for dietary trans, saturated, monounsaturated, and polyunsaturated fats, nor their aggregate adjustment or the P:S ratio. DLL effects persisted even adjusting for CRP (HR=1.29, P-trend=1 mg/dL for DLL (extreme quintile HR=1.38, 1.02-1.88), than among individuals with low CRP <1 mg/dl for DLL (HR=1.08, 0.68-1.72), with P-interaction<0.0001. Furthermore, CRP also modified DLI, where effects again diverged among higher CRP (HR=0.98, 0.73-1.31) versus low CRP (HR=0.45, 0.27-0.74), with P-interaction<0.0001. Moreover, adjustment of triglycerides, HbA1c, ICAM-1, LDL or HDL cholesterol also did not materially affect overall results. CONCLUSION: Results indicate that DLL is associated with increased risk of incident CHD, independent of traditional risk factors, conventional dietary fat classifications, and major CHD biomarkers. Effects of DLL and DLI appear to be modified by levels of CRP. DLL appears to be an important novel dietary fat index that captures additional CHD risk information beyond biomarkers and traditional dietary fat categories. Further studies are warranted.

Abstract P388: Novel Metabolic Markers for the Risk of Carotid Plaque Progression in American Indians

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yun Zhu ◽  
An Qiang ◽  
Lyle G Best ◽  
Elisa T Lee ◽  
Barbara V Howard ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Prediction ◽  
American Indians ◽  
Carotid Plaque ◽  
Plasma Metabolites ◽  
Plaque Progression ◽  
Cross Sectional ◽  
Metabolic Markers ◽  
Traditional Risk Factors

Background: Carotid atherosclerotic plaque and its progression significantly predict cardiovascular events. Traditional clinical factors have limited value in early risk prediction. Metabolomics is an emerging technology that can accurately quantify hundreds to thousands of small metabolites in biofluids, thus providing a powerful tool for early biomarker discovery. Previous studies were largely cross-sectional with a focus on the European population, results of which may not be generalized to other ethnic groups. In addition, causality cannot be resolved in cross-sectional analysis. Objective: To prospectively identify novel metabolic markers predictive of carotid plaque onset and progression in American Indians in the Strong Heart Study (SHS). Methods: This study includes 396 apparently healthy American Indians attending both clinical exams in 2001-2003 and 2006-2009 (average 5.5 years of follow-up). All participants had normal fasting glucose and were free of overt CVD at baseline. Plaque progression was defined as having a higher plaque score at the end of follow-up compared to baseline. Fasting plasma metabolites were detected using untargeted LC-MS. A total of 1,364 matching metabolites that passed stringent QC were included in the current analysis. The prospective association of plaque progression with each metabolite was examined using Cox proportional hazards model, adjusting for sex, site, age, BMI, eGFR, lipids, blood pressure, smoking and alcohol drinking at baseline. The combined metabolic effect was examined using a weighted multi-marker metabolites score comprising of all significant metabolites. Incremental value of novel metabolites over traditional risk factors for risk prediction was tested using the net reclassification improvement index (NRI). Multiple testing was corrected using the q-value method (q< 0.05 was considered statistical significance). Results: Of all 396 participants, 100 developed new plaque or progressed to a high order of atherosclerosis during follow-up. Five metabolites including PC (6:2/14:2) (HR 1.56[1.23-1.96]), proscillaridin A (HR 1.68 [1.27-2.21]), 8e-heptadecenedioic acid (HR 1.56 [1.22-1.98]), flavone (HR 1.69 [1.27-2.26]), and n-palmitoyl methionine (HR 1.72 [1.28-2.32]), significantly increase, whereas one metabolite, PC (18:0/18:1) (HR 0.62 [0.52-0.73]), significantly decreases the risk of plaque progression. A multi-marker score comprising of all six metabolites significantly improves risk prediction beyond traditional risk factors (NRI=0.22, P=1.23x10-5). Conclusions: Altered levels of fasting plasma metabolites significantly predict the risk of plaque onset and progression over and above conventional risk factors. The newly detected metabolites may unravel novel metabolic pathways underlying CVD pathogenesis and could be used as new markers for risk prediction and stratification.

scholarly journals Low ADAMTS13 activity is associated with an increased risk of ischemic stroke

Blood ◽  
2015 ◽  
Vol 126 (25) ◽  
pp. 2739-2746 ◽  
Author(s):  
Michelle A. H. Sonneveld ◽  
Moniek P. M. de Maat ◽  
Marileen L. P. Portegies ◽  
Maryam Kavousi ◽  
Albert Hofman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Stroke Risk ◽  
Adamts13 Activity ◽  
Increased Risk ◽  
Key Points ◽  
Ischemic Stroke Risk ◽  
Traditional Risk Factors

Key Points Low ADAMTS13 activity is associated with ischemic stroke. ADAMTS13 activity improved the accuracy of ischemic stroke risk predictions beyond the traditional risk factors.

Association of Protein Z Deficiency with Retinal Artery and Vein Occlusion.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3510-3510
Author(s):  
Maya Koren-Michowitz ◽  
Eva Eting ◽  
Yulia Voltchek ◽  
Naomi Rahimi-Levene ◽  
Osnat Garach-Jehoshua ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Study Group ◽  
Protein Z ◽  
Low Protein ◽  
Vein Occlusion ◽  
Increased Risk ◽  
Significant Difference ◽  
Retinal Artery ◽  
Traditional Risk Factors

Abstract Central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO) are common disorders mainly associated with traditional risk factors for atherosclerosis. There is no clear correlation between thrombophilia and CRVO. However it was suggested that hyperhomocysteinemia and the presence of antiphospholipid antibodies are risk factors for the development of CRAO. Protein Z is a vitamin K dependent cofactor for the inactivation of activated factor X (Xa) by the protein Z dependent protease inhibitor (ZPI). Protein Z deficiency presumably promotes thrombosis, in particular arterial thrombosis, as suggested by an association between low plasma protein Z levels and ischemic stroke. The similarity between risk factors for ischemic stroke and CRVO / CRAO and the fact that low protein Z levels are associated with an increased risk for ischemic stroke has led us to assess protein Z levels in patients with CRVO and CRAO. Plasma samples from 29 patients with CRVO and 7 patients with CRAO (total study group= 36, mean age 60±11) were screened for protein Z levels by ELISA. Study group was also screened for the presence of lupus anticoagulant (LAC) by the kaolin clotting time (KCT) index and the dilute Russells’ viper venum test (DRVVT), for activated protein C resistance (APCR) and anticardiolipin antibodies (ACA). Levels of protein Z were compared with a control group of 42 healthy individuals (mean age 43±11). Patients with CRAO and history of ischemic stroke or an embolic source were excluded. Thirty patients in the study group had traditional risk factors for atheroscalerosis including hypertension, diabetes mellitus, hyperlipidemia and smoking and 6 patients had none. There was no significant difference in protein Z levels between the whole study group patients and controls (1995±810 vs. 2010±603 ng/ml p=0.922). However, patients with no risk factors for CRVO/CRAO had significantly lower protein Z levels than controls (1379±682 vs. 2010±603 ng/ml p=0.022) and patients with risk factors (1379±682 vs. 2118±785 ng/ml p=0.04). In the study group three patients had abnormal APCR and 6 had positive LAC. There was no correlation between low protein Z levels and the presence of LAC, APCR or ACA, or a correlation between low protein Z levels and the specific diagnosis (CRVO or CRAO) or age. The data show that low protein Z levels may be an additional risk factor for CRVO and CRAO in patients without traditional risk factors for these disorders. The association should be explored in a larger group of patients.

scholarly journals Prevalence and determinants of diabetes and prediabetes in southwestern Iran: the Khuzestan comprehensive health study (KCHS)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sanam Hariri ◽  
Zahra Rahimi ◽  
Nahid Hashemi-Madani ◽  
Seyyed Ali Mard ◽  
Farnaz Hashemi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Waist Circumference ◽  
Multinomial Logistic Regression ◽  
Fasting Blood Glucose ◽  
Health Study ◽  
Khuzestan Province ◽  
Logistic Regression Models ◽  
Relative Risks ◽  
Southwestern Iran

Background The Middle East and North Africa (MENA) is postulated to have the highest increase in the prevalence of diabetes by 2030; however, studies on the epidemiology of diabetes are rather limited across the region, including in Iran. Methods This study was conducted between 2016 and 2018 among Iranian adults aged 20 to 65 years residing in Khuzestan province, southwestern Iran. Diabetes was defined as the fasting blood glucose (FBG) level of 126 mg/dl or higher, and/or taking antidiabetic medications, and/or self-declared diabetes. Prediabetes was defined as FBG 100 to 125 mg/dl. Multinomial logistic regression models were used to examine the association of multiple risk factors that attained significance on the outcome. Results Overall, 30,498 participants were recruited; the mean (±SD) age was 41.6 (±11.9) years. The prevalence of prediabetes and diabetes were 30.8 and 15.3%, respectively. We found a similar prevalence of diabetes in both sexes, although it was higher among illiterates, urban residents, married people, and smokers. Participants aged 50–65 and those with Body Mass Index (BMI) 30 kg/m2 or higher were more likely to be affected by diabetes [RR: 20.5 (18.1,23.3) and 3.2 (3.0,3.6)]. Hypertension [RR: 5.1 (4.7,5.5)], waist circumference (WC) equal or more than 90 cm [RR: 3.6 (3.3,3.9)], and family history [RR: 2.3 (2.2,2.5)] were also significantly associated with diabetes. For prediabetes, the main risk factors were age 50 to 65 years [RR: 2.6 (2.4,2.8)], BMI 30 kg/m2 or higher [RR: 1.9 (1.8,2.0)], hypertension and WC of 90 cm or higher [RR: 1.7 (1.6,1.8)]. The adjusted relative risks for all variables were higher in females than males, with the exception of family history for both conditions and waist circumference for prediabetes. Conclusions Prediabetes and diabetes are prevalent in southwestern Iran. The major determinants are older age, obesity, and the presence of hypertension. Further interventions are required to escalate diabetes prevention and diagnosis in high-risk areas across Iran.

scholarly journals Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Hsiang Lin ◽  
Oswald Ndi Nfor ◽  
Chien-Chang Ho ◽  
Shu-Yi Hsu ◽  
Disline Manli Tantoh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Alcohol Consumption ◽  
Genetic Variants ◽  
Regression Models ◽  
Hemorrhagic Stroke ◽  
Alcohol Exposure ◽  
Modifiable Risk Factors ◽  
Aldehyde Dehydrogenase 2 ◽  
Logistic Regression Models ◽  
Increased Risk

Abstract Background Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. Methods Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean  ±  SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p  <  0.0001). ALDH2 rs671 was not associated with either hemorrhagic or ischemic stroke among alcohol drinkers. However, the risk of developing hemorrhagic stroke was significantly higher among ADH1B rs1229984 TC  +  CC individuals who drank alcohol (odds ratio (OR), 4.85; 95% confidence interval (CI) 1.92–12.21). We found that the test for interaction was significant for alcohol exposure and rs1229984 genotypes (p for interaction  =  0.016). Stratification by alcohol exposure and ADH1B rs1229984 genotypes showed that the risk of developing hemorrhagic stroke remained significantly higher among alcohol drinkers with TC  +  CC genotype relative to those with the TT genotype (OR, 4.43, 95% CI 1.19–16.52). Conclusions Our study suggests that the ADH1B rs1229984 TC  +  CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

Traditional risk factors and combined genetic markers of recurrent ischemic stroke in adults

2021 ◽  
Author(s):  
Lamia M’barek ◽  
Salma Sakka ◽  
Fatma Megdiche ◽  
Nouha Farhat ◽  
Khadija Maalla ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Genetic Markers ◽  
Traditional Risk Factors

Abstract 14760: Myocardial Scarring by Magnetic Resonance Predicts Sudden Cardiac Death in Pediatric Patients With Hypertrophic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lars Grosse-Wortmann ◽  
Laurine van der Wal ◽  
Aswathy Vaikom House ◽  
Lee Benson ◽  
Raymond Chan
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Pediatric Patients ◽  
Risk Markers ◽  
C Statistic ◽  
Increased Risk ◽  
Traditional Risk Factors

Introduction: Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) has been shown to be an independent predictor of sudden cardiac death (SCD) in adults with hypertrophic cardiomyopathy (HCM). The clinical significance of LGE in pediatric HCM patients is unknown. Hypothesis: LGE improves the SCD risk prediction in children with HCM. Methods: We retrospectively analyzed the CMR images and reviewed the outcomes pediatric HCM patients. Results: Amongst the 720 patients from 30 centers, 73% were male, with a mean age of 14.2±4.8 years. During a mean follow up of 2.6±2.7 years (range 0-14.8 years), 34 experienced an episode of SCD or equivalent. LGE (Figure 1A) was present in 34%, with a mean burden of 14±21g, or 2.5±8.2g/m2 (6.2±7.7% of LV myocardium). The presence of ≥1 adult traditional risk factor (family history of SCD, syncope, LV thickness >30mm, non-sustained ventricular tachycardia on Holter) was associated with an increased risk of SCD (HR=4.6, p<0.0001). The HCM Risk-Kids score predicted SCD (p=0.002). The presence of LGE was strongly associated with an increased risk (HR=3.8, p=0.0003), even after adjusting for traditional risk factors (HR adj =3.2, p=0.003) or the HCM Risk-Kids score (HR adj =3.5, p=0.003). Furthermore, the burden of LGE was associated with increased risk (HR=2.1/10% LGE, p<0.0001). LGE burden remained independently associated with an increased risk for SCD after adjusting for traditional risk factors (HRadj=1.5/10% LGE, p=0.04) or HCM Risk-Kids (HRadj=1.9/10% LGE, p=0.0018, Figure 1B). The addition of LGE burden improved the predictive model using traditional risk markers (C statistic 0.67 vs 0.77, p=0.003) and HCM Risk-Kids (C statistic 0.68 vs 0.74, p=0.045). Conclusions: Quantitative LGE is an independent risk factor for SCD in pediatric patients with HCM and improves the performance of traditional risk markers and the HCM Risk-Kids Score for SCD risk stratification in this population.

scholarly journals Risk factors for macular pucker after rhegmatogenous retinal detachment surgery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Toshiaki Hirakata ◽  
Yoshimune Hiratsuka ◽  
Shutaro Yamamoto ◽  
Koki Kanbayashi ◽  
Hiroaki Kobayashi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Retinal Detachment ◽  
Surgical Technique ◽  
Regression Models ◽  
Rhegmatogenous Retinal Detachment ◽  
Surgical Repair ◽  
Macular Pucker ◽  
Logistic Regression Models ◽  
Retinal Breaks ◽  
Increased Risk

AbstractMacular pucker, also known as an epiretinal membrane, sometimes forms after surgical repair of a rhegmatogenous retinal detachment (RRD) and can decrease visual acuity and cause aniseikonia. However, few reports are evaluating the risk factors of macular pucker using multivariate analysis. To evaluate the risk factors for macular pucker after RRD surgery, 226 patients who underwent RRD surgery and were monitored for greater than 12 months (23.2 ± 6.4 months) after surgery were analyzed retrospectively. Of these cases, macular pucker developed in 26 cases. Multiple logistic regression models of 22 clinical characteristics were performed. An increased risk of macular pucker after RRD surgery was significantly associated with preoperative vitreous haemorrhage (Odds ratio (OR), 4.71; 95% CI 1.19–18.62), multiple retinal breaks (OR, 8.07; 95% CI 2.35–27.71), re-detachment (OR, 19.66; 95% CI 4.87–79.38), and retinal detachment area (OR, 12.91; 95% CI 2.34–71.19). Macular pucker was not associated with the surgical technique. Regardless of the surgical technique used, careful observation for postoperative macular pucker is needed after RRD surgery in high-risk cases. These findings can be used to improve the surgical management of patients with RRD. (183 words).

scholarly journals Polygenic risk prediction models for colorectal cancer: a systematic review

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Michele Sassano ◽  
Marco Mariani ◽  
Gianluigi Quaranta ◽  
Roberta Pastorino ◽  
Stefania Boccia
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Systematic Review ◽  
Prediction Model ◽  
Risk Prediction ◽  
Genetic Variants ◽  
Prediction Models ◽  
Risk Prediction Models ◽  
Discriminatory Accuracy ◽  
Traditional Risk Factors

Abstract Background Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors. Methods We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement. Results We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry. Conclusions Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed.

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