SU112DOES POLYGENIC RISK SCORE FOR SCHIZOPHRENIA IMPACT ON JUMPING TO CONCLUSIONS? PRELIMINARY FINDINGS FROM THE EU-GEI CASE-CONTROL STUDY

2019 ◽  
Vol 29 ◽  
pp. S1326
Author(s):  
Giada Tripoli ◽  
Diego Quattrone ◽  
Charlotte Gayer-Anderson ◽  
Victoria Rodríguez ◽  
Natasha Benzian-Olsson ◽  
...  
2019 ◽  
Vol 45 (Supplement_2) ◽  
pp. S219-S220 ◽  
Author(s):  
Giada Tripoli ◽  
Diego Quattrone ◽  
Graham Murray ◽  
Charlotte Gayer-Anderson ◽  
Victoria Rodriguez ◽  
...  

Author(s):  
Cheng Peng ◽  
Chi Gao ◽  
Donghao Lu ◽  
Bernard A Rosner ◽  
Oana Zeleznik ◽  
...  

ABSTRACT Background Carotenoids represent 1 of few modifiable factors to reduce breast cancer risk. Elucidation of interactions between circulating carotenoids and genetic predispositions or mammographic density (MD) may help inform more effective primary preventive strategies in high-risk populations. Objectives We tested whether women at high risk for breast cancer due to genetic predispositions or high MD would experience meaningful and greater risk reduction from higher circulating levels of carotenoids in a nested case-control study in the Nurses’ Health Studies (NHS and NHSII). Methods This study included 1919 cases and 1695 controls in a nested case-control study in the NHS and NHSII. We assessed both multiplicative and additive interactions. RR reductions and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors. Absolute risk reductions (ARR) were calculated based on Surveillance, Epidemiology, and End Results incidence rates. Results We showed that compared with women at low genetic risk or low MD, those with higher genetic risk scores or high MD had greater ARRs for breast cancer as circulating carotenoid levels increase (additive P-interaction = 0.05). Among women with a high polygenic risk score, those in the highest quartile of circulating carotenoids had a significant ARR (28.6%; 95% CI, 14.8–42.1%) compared to those in the lowest quartile of carotenoids. For women with a high percentage MD (≥50%), circulating carotenoids were associated with a 37.1% ARR (95% CI, 21.7–52.1%) when comparing the highest to the lowest quartiles of circulating carotenoids. Conclusions The inverse associations between circulating carotenoids and breast cancer risk appeared to be more pronounced in high-risk women, as defined by germline genetic makeup or MD.


CJEM ◽  
2018 ◽  
Vol 20 (S1) ◽  
pp. S17-S18
Author(s):  
R. Ohle ◽  
S. McIsaac ◽  
J. J. Perry

Introduction: Acute aortic dissection (AAD) is a rare but fatal condition where over-investigation and missed diagnosis are common. Our objectives were to derive a highly sensitive clinical risk score for AAD and perform pilot validation. Methods: We started with two independent systemic reviews to firstly identify clinical variables associated with AAD and secondly to determine reasons for missed diagnosis. We searched Medline, Embase and the Cochrane database (1968-July 2016). Two reviewers screened articles and extracted data. Agreement was measured by Kappa and study quality by the QUADAS-2 tool. Bivariate random-effects meta-analyses (Revman 5 and SAS 9.3) were performed. Due to sampling bias found in the systematic reviews a matched case control study confirming the strength and direction of predictor variables was performed. The cases (2002-2014) included new emergency department (ED) or in-hospital diagnosis of non-traumatic AAD confirmed by computed tomography (CT). The controls (2010-2011) were a random age/sex matched sample of patients triaged with undifferentiated acute truncal pain (< 14 days). Finally, we used the beta coefficients derived from multivariate logistic regression of our case control study to assign a numerical strength of association to predictor variables. To mitigate the bias inherent in case control studies we adjusted the beta coefficient for each variable by the diagnostic odds ratio calculated from each systematic review. Pilot validation was performed on a retrospective sample of all those undergoing CTA to rule out AAD at two tertiary care ED over 12 months. Two abstractors were blinded to the final diagnosis. Results: We derived a two-step risk score based on the derivation sample which included 4960 patients(Clinical variables systematic review -9 studies, N=2400, low risk of bias, Kappa 0.9 & Reasons for missed diagnosis systematic review - 11 studies, N=800, low-moderate risk of bias, Kappa 0.89 & Case control study -194 AAD, 776 Controls). Step one is a RAPID assessment for AAD 1) Risk factors 2) Alternative diagnosis in the differential that mimics AAD- ACS, PE, Stroke 3) Physical exam- hypotension, pulse deficit 4) Impression- clinical suspicion of AAD and 5) Discomfort- migrating, tearing, pleuritic, thunderclap, severe pain. If any of the above factors are present proceed to step two. Step two stratifies patients based on history (low, moderate, high suspicion), physical exam (hypotension/pulse deficit) and risk factors. In the pilot validation (N=375,AAD=16) sensitivity was 100% (95%CI 79.4-100) and specificity 36.5% (95%CI 31.5-41.7%). Patients were successfully stratified into low (<2, 0% AAD), moderate (2, 2.2% AAD), high (>2, 19.6% AAD) and critical probability (>3, 62.5% AAD), with up to 36% reduction in imaging. Conclusion: We derived a highly sensitive new clinical risk score with the potential to reduce missed cases of AAD, reduce unnecessary imaging and expedite care.


2020 ◽  
pp. 1-11 ◽  
Author(s):  
Giada Tripoli ◽  
Diego Quattrone ◽  
Laura Ferraro ◽  
Charlotte Gayer-Anderson ◽  
Victoria Rodriguez ◽  
...  

Abstract Background The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ. Methods A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia. Results The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients. Conclusions Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.


2014 ◽  
Vol 165 (4) ◽  
pp. 793-798 ◽  
Author(s):  
Christie M. Atchison ◽  
Shilpa Arlikar ◽  
Ernest Amankwah ◽  
Irmel Ayala ◽  
Laurie Barrett ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18162-e18162
Author(s):  
Omar El Charif ◽  
Heather E. Wheeler ◽  
Matthew Trendowski ◽  
Eric R Gamazon ◽  
Shirin Ardeshirrouhanifard ◽  
...  

e18162 Background: RP is an adverse drug reaction characterized by reduced blood flow to the extremities causing pain and sensations of cold. Few studies have examined the genetic basis for RP, although family studies suggest a heritable component to primary RP. Methods: Eligible testicular cancer survivors (TCS) were < 55 y at diagnosis, treated with first line cisplatin-based chemotherapy, and completed questionnaires. Genotyping with standard quality control and imputation were performed. A case-control RP phenotype was derived from patient-reported outcomes and associations were computed by logistic regression. GWAS used cumulative bleomycin dose and 10 genetic principal components as covariates. Gene set enrichment analysis (GSEA) utilized genes ranked by the most significant GWAS SNP in/within 20 kilobases. A polygenic risk score for CVD derived from four prior independent GWAS (Khera et al. NEJM 2016) was assessed for association with RP. Results: Of 749 patients (median age 38 y, median time since chemotherapy 5 y), 38% reported RP. Bleomycin dose was the most significant predictor of RP (OR100 mg/m2 = 1.25, p < 0.0001). Number of years smoking also correlated with RP (ORyear = 1.05, p = 0.002). Age and hypertension showed no significant correlation with RP. GSEA revealed several significant pathways (FDR q < 0.1), including “ cellular response to VEGF stimulus” (q = 0.05) and “ cardiac muscle cell action potential” (q = 0.09). We hypothesized that RP may share genetic architecture with CVD. Deriving a polygenic risk score from genome-wide significant SNPs in prior CVD GWAS (n = 4260-22,389), we showed nearly significant case-control differences in CVD polygenic risk score (two-tailed t-test, p = 0.053). RP frequency significantly increased with polygenic risk score quartile (OR = 1.19, p = 0.008). Conclusions: Over one third of TCS report RP, with greater frequency among bleomycin-treated patients and smokers. Implicated genetic pathways include ones established in CVD. Although shared genetic risk between chemotherapy-induced RP and CVD may be possible, further investigation is required. Primary RP has been inconsistently linked with CVD.


Author(s):  
Arianna Di Florio ◽  
Jessica Mei Kay Yang ◽  
Karen Crawford ◽  
Veerle Bergink ◽  
Ganna Leonenko ◽  
...  

2014 ◽  
Vol 23 (7) ◽  
pp. 969-974 ◽  
Author(s):  
Cristiano Fava ◽  
Marketa Sjögren ◽  
Sandra Olsson ◽  
Håkan Lövkvist ◽  
Katarina Jood ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document