Polygenic risk scores

Watson, Roger

doi:10.1111/jan.14020

Cited by 2 publications

(1 citation statement)

References 5 publications

(9 reference statements)

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“…We hypothesize that the joint association of several BP genes of different pathways on SS is stronger than that of individual genetic variants. A polygenic risk score (PRS) indicates the likelihood of an outcome developing due to a person's genome and can reflect a general genetic susceptibility of a certain disease [8]. To date, evidence regarding the association between the PRS and salt sensitivity remains limited, and the results are inconsistent (see below).…”

Section: Introductionmentioning

confidence: 99%

Genetic Predisposition and Salt Sensitivity in a Chinese Han Population: The EpiSS Study

Liu

et al. 2020

International Journal of Hypertension

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Objectives. Genome-wide association studies and candidate gene studies have found many single nucleotide polymorphisms (SNPs) that affect salt sensitivity (SS). We constructed a polygenic risk score (PRS) to estimate the joint effect of these SNPs on SS. Methods. We recruited 762 Chinese participants into the study. An unweighted PRS was constructed using 42 known genetic risk variants associated with SS or salt sensitivity blood pressure. A modified Sullivan’s acute oral saline load and diuresis shrinkage test was used to detect salt sensitivity. Logistic regression was used to estimate the joint effect of the SNPs on SS both overall and after stratification by hypertension. Results. The mean age of the participants was 57.1 years, and most of them were female (77.4%). The prevalence of SS was 28.7%. Both the continuous PRS and PRS tertiles were significantly associated with the risk of SS and a BP increase of more than 5 mmHg during acute salt loading but were not associated with a BP decrease of more than 10 mmHg during the diuresis shrinkage process. In the normotensive group, participants with PRSs in the middle and top tertiles had a more than twofold increased risk of SS (OR = 2.18, 95% CI: 1.15–4.12, P=0.016, and OR = 2.28, 95% CI: 1.19–4.38, P=0.013, respectively) compared with participants with PRSs in the first tertile. In the normotensive group, participants with PRSs in the middle tertile (OR = 1.94, 95% CI: 1.01–3.71, P=0.046) and top tertile (OR = 2.30, 95% CI: 1.19–4.44, P=0.013) had an increased risk of a greater than 5 mmHg increase in BP during acute salt loading than those with PRSs in the first tertile. In the hypertension group, neither the continuous PRS nor PRS tertile was significantly associated with the risk of SS. Conclusion. The 42 investigated SNPs were jointly and significantly associated with SS, especially in the normotensive Chinese population. These findings may provide genetic evidence for identifying target populations that would benefit from salt restriction policies.

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Section: Introductionmentioning

confidence: 99%

Genetic Predisposition and Salt Sensitivity in a Chinese Han Population: The EpiSS Study

Liu

et al. 2020

International Journal of Hypertension

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A stable and adaptive polygenic signal detection method based on repeated sample splitting

Zhao¹,

Sun²

2020

Preprint

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Using polygenic risk score for trait association analyses and disease prediction are paramount for genetic studies of complex traits. Valid inference relies on sample splitting, or more recently external data, to obtain a set of potentially associated genetic variants, along with their weights, for polygenic risk score construction. The use of external data has been popular, but recent work increasingly calls its use into question due to adverse effects of potential data heterogeneity between different samples. Our study here adheres to the original sampling-splitting principle but does so, repeatedly, to increase stability of our inference. To accommodate different polygenic structures, we develop an adaptive test for generalized linear models. We provide the asymptotic null distributions of the proposed test for both fixed and diverging number of variants. We also show the asymptotic properties of the proposed test under local alternatives, providing insights on why power gain attributed to variable selection and weighting can compensate for efficiency loss due to sample splitting. We support our analytical findings through extensive simulation studies and an application.

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Polygenic risk scores

Cited by 2 publications

References 5 publications

Genetic Predisposition and Salt Sensitivity in a Chinese Han Population: The EpiSS Study

Genetic Predisposition and Salt Sensitivity in a Chinese Han Population: The EpiSS Study

A stable and adaptive polygenic signal detection method based on repeated sample splitting

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