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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
Surendran, P, Feofanova, EV, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, et al
Nature genetics. 2020;(12):1314-1332
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Abstract
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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Public health monitoring of hypertension, diabetes and elevated cholesterol: comparison of different data sources.
Paalanen, L, Koponen, P, Laatikainen, T, Tolonen, H
European journal of public health. 2018;(4):754-765
Abstract
BACKGROUND Three data sources are generally used in monitoring health on the population level. Health interview surveys (HISs) are based on participants' self-report. Health examination surveys (HESs) yield more objective data, and also persons who are unaware of their elevated risks can be detected. Medical records (MRs) and other administrative registers also provide objective data, but their availability, coverage and quality vary between countries. We summarized studies comparing self-reported data with (i) measured data from HESs or (ii) MRs. We aimed to describe differences in feasibility and comparability of different data sources for monitoring (i) elevated blood pressure or hypertension (ii) elevated blood glucose or diabetes and (iii) elevated total cholesterol. METHODS We conducted a literature search to identify studies, which validated self-reported measures against objective measures. We found 30 studies published since the year 2000 fulfilling our inclusion criteria (targeted to adults and comparing prevalence among the same persons). RESULTS Hypertension and elevated total cholesterol were prone to be under-estimated in HISs. The under-estimate was more pronounced, when the HIS data were compared with HES data, and lower when compared with MRs. For diabetes, the HISs and the objective methods resulted in fairly similar prevalence rates. CONCLUSION The three data sources measure different manifestations of the risk factors and cannot be expected to yield similar prevalence rates. Using HIS data only may lead to under-estimation of elevated risk factor levels or disease prevalence. Whenever possible, information from the three data sources should be evaluated and combined.