This readme accompanies the paper "Genetic susceptibility loci for cardiovascular disease and their impact on atherosclerotic plaques." by Van der Laan S.W. et al. Journal 2018.
Background Atherosclerosis is a chronic inflammatory disease in part caused by lipid uptake in the vascular wall, but the exact underlying mechanisms leading to acute myocardial infarction and stroke remain poorly understood. Large consortia identified genetic susceptibility loci that associate with large artery ischemic stroke (LAS) and coronary artery disease (CAD). However, deciphering their underlying mechanisms is challenging. Histological studies identified destabilizing characteristics in human atherosclerotic plaques that associate with clinical outcome. To what extent established susceptibility loci for LAS and CAD relate to plaque characteristics is thus far unknown but may point to novel mechanisms.
Methods We studied the associations of 61 established cardiovascular risk loci with 7 histological plaque characteristics assessed in 1,443 carotid plaque specimens from the Athero-Express Biobank Study. We also assessed if the genotyped cardiovascular risk loci impact the tissue-specific gene expression in two independent biobanks, BiKE and STAGE.
Results A total of 21 established risk variants (out of 61) nominally associated to a plaque characteristic. One variant (rs12539895, risk allele A) at 7q22 associated to a reduction of intraplaque fat, p = 5.09x10-6 after correction for multiple testing. We further characterized this 7q22 locus and show tissue-specific effects of rs12539895 on HBP1 expression in plaques and COG5 expression in whole blood, and provide data from public resources showing an association with decreased LDL and increase HDL in the blood.
Conclusions Our study supports the view that cardiovascular susceptibility loci may exert their effect by influencing the atherosclerotic plaque characteristics.
For this I used mainly GWASToolKit. Some additional useful scripts I used are found in the HerculesToolKit. The polygenic (risk) scores were made with a script we (Jessica van Setten and I) had gotten via Eli Stahl. All (raw) genotype data will be made available soon via EGA; a link is supplied above.
Scripts will work within the context of a certain Linux environment, for example a CentOS7 system on a SUN Grid Engine background or macOS X Lion+ (version 10.7.[x]+).
Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions:
The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software.
THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.
Reference: http://opensource.org.