PT  - JOURNAL ARTICLE
AU  - Xu Chen
AU  - Solmaz Yazdani
AU  - Fredrik Piehl
AU  - Patrik K.E. Magnusson
AU  - Fang Fang
TI  - Polygenic Link between Blood Lipids and Amyotrophic Lateral Sclerosis
AID  - 10.1101/138156
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 138156
4099  - http://biorxiv.org/content/early/2017/05/17/138156.short
4100  - http://biorxiv.org/content/early/2017/05/17/138156.full
AB  - Dyslipidemia is common among patients with amyotrophic lateral sclerosis (ALS), but the genetic evidence for the link between blood lipids and ALS is unclear. We assessed the associations of polygenic risk scores (PRS) for low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) with ALS, using summary results from genome-wide association studies. PRS of LDL-C (OR=1.17; 95%CI 1.11-1.23) and TC (OR=1.15; 95%CI 1.09-1.21) were significantly associated with a higher risk of ALS, whereas no association was noted for PRS of TG and HDL-C. Although linkage disequilibrium score regression indicated weak genetic correlations between lipids and ALS, several genetic variants known to up-regulate LDL-C and TC levels were shown to be associated with a higher risk of ALS. This study demonstrates a clear polygenic link between LDL-C, TC and ALS, and suggests that inherited dyslipidemia might be an etiological part of ALS development.Acknowledgement statement (including conflict of interest and funding sources) We would like to thank the following consortia for sharing their summary GWAS results: the Global Lipids Genetics Consortium, CARDIoGRAMplusC4D Consortium and Project MinE GWAS Consortium. The authors declare no conflicts of interest. This study was funded by the Swedish Research Council (grant no. 2015-03170), the Karolinska Institutet (Senior Researcher Award and Strategic Research Program in Epidemiology), and the Ulla-Carin Lindquist Foundation.