Leveraging genetic discoveries for sleep to determine causal relationships with common complex traits

Sleep

article

Sonti, Shilpa¹  Grant, Struan F A¹ 

[1] Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia;Department of Genetics, University of Pennsylvania;Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania;Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine;Division of Human Genetics and Endocrinology, Children’s Hospital of Philadelphia

关键词: Mendelian Randomization;    GWAS;    Sleep disorders;    Insomnia;    Sleep duration;    Narcolepsy;    Obstructive Sleep apnea (OSA);    Restless leg syndrome (RLS);    Neurodegenerative disorders;    Cardiovascular disorders;    obesity;    cancer;   

DOI  :  10.1093/sleep/zsac180

学科分类：生理学

来源: American Academy of Sleep Medicine

【 摘 要 】

Sleep occurs universally and is a biological necessity for human functioning. The consequences of diminished sleep quality impact physical and physiological systems such as neurological, cardiovascular, and metabolic processes. In fact, people impacted by common complex diseases experience a wide range of sleep disturbances. It is challenging to uncover the underlying molecular mechanisms responsible for decreased sleep quality in many disease systems owing to the lack of suitable sleep biomarkers. However, the discovery of a genetic component to sleep patterns has opened a new opportunity to examine and understand the involvement of sleep in many disease states. It is now possible to use major genomic resources and technologies to uncover genetic contributions to many common diseases. Large scale prospective studies such as the genome wide association studies (GWAS) have successfully revealed many robust genetic signals associated with sleep-related traits. With the discovery of these genetic variants, a major objective of the community has been to investigate whether sleep-related traits are associated with disease pathogenesis and other health complications. Mendelian Randomization (MR) represents an analytical method that leverages genetic loci as proxy indicators to establish causal effect between sleep traits and disease outcomes. Given such variants are randomly inherited at birth, confounding bias is eliminated with MR analysis, thus demonstrating evidence of causal relationships that can be used for drug development and to prioritize clinical trials. In this review, we outline the results of MR analyses performed to date on sleep traits in relation to a multitude of common complex diseases.

【 授权许可】

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