@article {Chen138156, author = {Xu Chen and Solmaz Yazdani and Fredrik Piehl and Patrik K.E. Magnusson and Fang Fang}, title = {Polygenic Link between Blood Lipids and Amyotrophic Lateral Sclerosis}, elocation-id = {138156}, year = {2017}, doi = {10.1101/138156}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2017/05/17/138156.1}, eprint = {https://www.biorxiv.org/content/early/2017/05/17/138156.1.full.pdf}, journal = {bioRxiv} }