Author:
Zhao Yangfan,Gagliano Taliun Sarah A.
Abstract
Parkinson's disease (PD) affects millions of individuals worldwide, and it is the second most common late-onset neurodegenerative disorder. There is no cure and current treatments only alleviate symptoms. Modifiable risk factors have been explored as possible options for decreasing risk or developing drug targets to treat PD, including low-density lipoprotein cholesterol (LDL-C). There is evidence of sex differences for cholesterol levels as well as for PD risk. Genetic datasets of increasing size are permitting association analyses with increased power, including sex-stratified analyses. These association results empower Mendelian randomization (MR) studies, which, given certain assumptions, test whether there is a causal relationship between the risk factor and the outcome using genetic instruments. Sex-specific causal inference approaches could highlight sex-specific effects that may otherwise be masked by sex-agnostic approaches. We conducted a sex-specific two-sample cis-MR analysis based on genetic variants in LDL-C target encoding genes to assess the impact of lipid-lowering drug targets on PD risk. To complement the cis-MR analysis, we also conducted a sex-specific standard MR analysis (using genome-wide independent variants). We did not find evidence of a causal relationship between LDL-C levels and PD risk in females [OR (95% CI) = 1.01 (0.60, 1.69), IVW random-effects] or males [OR (95% CI) = 0.93 (0.55, 1.56)]. The sex-specific standard MR analysis also supported this conclusion. We encourage future work assessing sex-specific effects using causal inference techniques to better understand factors that may contribute to complex disease risk differently between the sexes.
Subject
Neurology (clinical),Neurology
Reference120 articles.
1. Alzheimer's disease and Parkinson's disease;Nussbaum;N Engl J Med.,2003
2. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016;Collaborators;Lancet Neurol.,2019
3. Diagnosis and treatment of parkinson disease: a review;Armstrong;JAMA.,2020
4. Striatal synapses, circuits, and Parkinson's disease;Zhai;Curr Opin Neurobiol.,2018
5. Parkinson's disease;Bloem;Lancet.,2021
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献