Generalization of a genetic risk score for time to first albuminuria in children with sickle cell anaemia: SCCRIP cohort study results

Author(s):  
Sara R. Rashkin ◽  
Evadnie Rampersaud ◽  
Guolian Kang ◽  
Kenneth I. Ataga ◽  
Jane S. Hankins ◽  
...  
PLoS Medicine ◽  
2018 ◽  
Vol 15 (3) ◽  
pp. e1002525 ◽  
Author(s):  
Evan D. Muse ◽  
Nathan E. Wineinger ◽  
Emily G. Spencer ◽  
Melissa Peters ◽  
Riley Henderson ◽  
...  

2020 ◽  
Vol 105 (4) ◽  
pp. 1242-1250
Author(s):  
Xu Han ◽  
Yue Wei ◽  
Hua Hu ◽  
Jing Wang ◽  
Zhaoyang Li ◽  
...  

Abstract Objective The objective of this study is to examine whether healthy lifestyle could reduce diabetes risk among individuals with different genetic profiles. Design A prospective cohort study with a median follow-up of 4.6 years from the Dongfeng-Tongji cohort was performed. Participants A total of 19 005 individuals without diabetes at baseline participated in the study. Main Variable Measure A healthy lifestyle was determined based on 6 factors: nonsmoker, nondrinker, healthy diet, body mass index of 18.5 to 23.9 kg/m2, waist circumference less than 85 cm for men and less than 80 cm for women, and higher level of physical activity. Associations of combined lifestyle factors and incident diabetes were estimated using Cox proportional hazard regression. A polygenic risk score of 88 single-nucleotide polymorphisms previously associated with diabetes was constructed to test for association with diabetes risk among 7344 individuals, using logistic regression. Results A total of 1555 incident diabetes were ascertained. Per SD increment of simple and weighted genetic risk score was associated with a 1.39- and 1.34-fold higher diabetes risk, respectively. Compared with poor lifestyle, intermediate and ideal lifestyle were reduced to a 23% and 46% risk of incident diabetes, respectively. Association of lifestyle with diabetes risk was independent of genetic risk. Even among individuals with high genetic risk, intermediate and ideal lifestyle were separately associated with a 29% and 49% lower risk of diabetes. Conclusion Genetic and combined lifestyle factors were independently associated with diabetes risk. A healthy lifestyle could lower diabetes risk across different genetic risk categories, emphasizing the benefit of entire populations adhering to a healthy lifestyle.


Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 75979-75988 ◽  
Author(s):  
Jong Jin Oh ◽  
Seunghyun Park ◽  
Sang Eun Lee ◽  
Sung Kyu Hong ◽  
Sangchul Lee ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1535-P
Author(s):  
RACHEL G. MILLER ◽  
TINA COSTACOU ◽  
SUNA ONENGUT-GUMUSCU ◽  
WEI-MIN CHEN ◽  
STEPHEN S. RICH ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ganna Leonenko ◽  
Emily Baker ◽  
Joshua Stevenson-Hoare ◽  
Annerieke Sierksma ◽  
Mark Fiers ◽  
...  

AbstractPolygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, how to model the effect of APOE, what the optimal p-value threshold (pT) for SNP selection is and how to compare scores between studies and methods. We show that the best prediction accuracy is achieved with a model with two predictors (APOE and PRS excluding APOE region) with pT<0.1 for SNP selection. Prediction accuracy in a sample across different PRS approaches is similar, but individuals’ scores and their associated ranking differ. We show that standardising PRS against the population mean, as opposed to the sample mean, makes the individuals’ scores comparable between studies. Our work highlights the best strategies for polygenic profiling when assessing individuals for AD risk.


JAMA ◽  
2016 ◽  
Vol 316 (17) ◽  
pp. 1825
Author(s):  
Marcus R. Munafò ◽  
Kate Tilling ◽  
George Davey Smith

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