Causal effects of blood lipids on amyotrophic lateral sclerosis: a Mendelian randomization study

Year: 2018

Type: article

Abstract: Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disorder that is predicted to increase across the globe by ~70% in the following decades. Understanding the disease causal mechanism underlying ALS and identifying modifiable risks factors for ALS hold the key for the development of effective preventative and treatment strategies. Here, we investigate the causal effects of four blood lipid traits that include high-density lipoprotein, low-density lipoprotein (LDL), total cholesterol and triglycerides on the risk of ALS. By leveraging instrument variables from multiple large-scale genome-wide association studies in both European and East Asian populations, we carry out one of the largest and most comprehensive Mendelian randomization analyses performed to date on the causal relationship between lipids and ALS. Among the four lipids, we found that only LDL is causally associated with ALS and that higher LDL level increases the risk of ALS in both the European and East Asian populations. Specifically, the odds ratio of ALS per 1 standard deviation (i.e. 39.0 mg/dL) increase of LDL is estimated to be 1.14 [95% confidence interval (CI), 1.05-1.24; P = 1.38E-3] in the European population and 1.06 (95% CI, 1.00-1.12; P = 0.044) in the East Asian population. The identified causal relationship between LDL and ALS is robust with respect to the choice of statistical methods and is validated through extensive sensitivity analyses that guard against various model assumption violations. Our study provides important evidence supporting the causal role of higher LDL on increasing the risk of ALS, paving ways for the development of preventative strategies for reducing the disease burden of ALS across multiple nations.

Source: Human Molecular Genetics

DOI: 10.1093/hmg/ddy384

Authors: Ping Zeng, Xiang Zhou

Institutions: Xuzhou Medical College, University of Michigan

Language: English

Topic: Amyotrophic Lateral Sclerosis Research

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,390

Funders: National Science Foundation, Youth Foundation, National Bureau of Statistics of China, National Natural Science Foundation of China, Ministry of Education of the People's Republic of China, China Postdoctoral Science Foundation, Natural Science Foundation of Jiangsu Province, Xuzhou Medical University, Priority Academic Program Development of Jiangsu Higher Education Institutions, National Institutes of Health, National Human Genome Research Institute

OpenAlex ID: W2952420414