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Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders.

ABSTRACT: Clinical and epidemiological studies have shown that circulatory system diseases and nervous system disorders often co-occur in patients. However, genetic susceptibility factors shared between these disease categories remain largely unknown. Here, we characterized pleiotropy across 107 circulatory system and 40 nervous system traits using an ensemble of methods in the eMERGE Network and UK Biobank. Using a formal test of pleiotropy, five genomic loci demonstrated statistically significant evidence of pleiotropy. We observed region-specific patterns of direction of genetic effects for the two disease categories, suggesting potential antagonistic and synergistic pleiotropy. Our findings provide insights into the relationship between circulatory system diseases and nervous system disorders which can provide context for future prevention and treatment strategies.

SUBMITTER: Zhang X

PROVIDER: S-EPMC9198016 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders.

Zhang Xinyuan X Lucas Anastasia M AM Veturi Yogasudha Y Drivas Theodore G TG Bone William P WP Verma Anurag A Chung Wendy K WK Crosslin David D Denny Joshua C JC Hebbring Scott S Jarvik Gail P GP Kullo Iftikhar I Larson Eric B EB Rasmussen-Torvik Laura J LJ Schaid Daniel J DJ Smoller Jordan W JW Stanaway Ian B IB Wei Wei-Qi WQ Weng Chunhua C Ritchie Marylyn D MD

Nature communications 20220614 1

Clinical and epidemiological studies have shown that circulatory system diseases and nervous system disorders often co-occur in patients. However, genetic susceptibility factors shared between these disease categories remain largely unknown. Here, we characterized pleiotropy across 107 circulatory system and 40 nervous system traits using an ensemble of methods in the eMERGE Network and UK Biobank. Using a formal test of pleiotropy, five genomic loci demonstrated statistically significant eviden ...[more]

PMID: 35701404

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Project description:Aims and Objectives: The autonomic nervous system plays an important role in homeostasis and organismic recreation, control of immune function, inflammation, and bone growth. It also regulates blood pressure and orthostasis via vagal and sympathetic pathways. Besides recording of heart rate variability (HRV), which characterizes medium (1-5 min) and long term (circadian) autonomic tone or modulation, no gentle tests of short-term autonomic reactivity and control are available. In 1976 Nogier described a short time cardiovascular response ("Réflexe Auriculo Cardiaque", RAC) which could be used to investigate short term autonomic reactions without changing system characteristics and thus being repeatable in short intervals. In this paper, we investigated the possible application of the Nogier reaction as a micro-test for the identification of a disturbed sensitivity or reactivity of the autonomic nervous system. Methods: We statistically analyzed cardiovascular signals derived during the application of small repeated stimuli utilizing methods of signal averaging to characterize the physiological background. Specifically, the Nogier reaction was investigated using simultaneous recordings of ECG, pulse waves, and respiration. Results: Significant fast (delay 1-5 s) and slower (delay 6-12 s) cardio-autonomic responses to different stimuli which characterize short term were observed. From time characteristics and type of signals where they occur we deduce that fast changes observed in heart rate are vagal reactions to the small stimuli whereas slower changes observed in pulse waves stem from sympathetic nervous system responses. Conclusions: The investigated autonomic micro-test opens the possibility to differentially investigate both limbs of the autonomic nervous system with minimal stimuli. It can be performed within seconds and does not change the set point of the system in opposition to less subtle tests such as Valsalva maneuver. Therefore, it is well-suited for quick, repeated measurements of autonomic nervous system reactivity.

Dataset Information

Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders.

Publications

Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders.

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