| Title: |
Rare missense functional variants at COL4A1 and COL4A2 in sporadic intracerebral hemorrhage |
| Authors: |
Chung, Jaeyoon; Hamilton, Graham; Kim, Minsup; Marini, Sandro; Montgomery, Bailey; Henry, Jonathan; Cho, Art E.; Brown, Devin L.; Worrall, Bradford B.; Meschia, James F.; Silliman, Scott L.; Selim, Magdy; Tirschwell, David L.; Kidwell, Chelsea S.; Kissela, Brett; Greenberg, Steven M.; Viswanathan, Anand; Goldstein, Joshua N.; Langefeld, Carl D.; Rannikmae, Kristiina; Sudlow, Catherine L.M.; Samarasekera, Neshika; Rodrigues, Mark; Al-Shahi Salman, Rustam; Prendergast, James G.D.; Harris, Sarah E.; Deary, Ian; Woo, Daniel; Rosand, Jonathan; Van Agtmael, Tom; Anderson, Christopher D. |
| Publisher Information: |
American Academy of Neurology |
| Publication Year: |
2021 |
| Collection: |
University of Glasgow: Enlighten - Publications |
| Description: |
Objective: To test the genetic contribution of rare missense variants in COL4A1 and COL4A2 in which common variants are genetically associated with sporadic intracerebral hemorrhage (ICH), we performed rare variant analysis in multiple sequencing data for the risk for sporadic ICH. Methods: We performed sequencing across 559Kbp at 13q34 including COL4A1 and COL4A2 among 2,133 individuals (1,055 ICH cases; 1,078 controls) in US-based and 1,492 individuals (192 ICH cases; 1,189 controls) from Scotland-based cohorts, followed by sequence annotation, functional impact prediction, genetic association testing, and in silico thermodynamic modeling. Results: We identified 107 rare nonsynonymous variants in sporadic ICH, of which two missense variants, rs138269346 (COL4A1I110T) and rs201716258 (COL4A2H203L), were predicted to be highly functional and occurred in multiple ICH cases but not in controls from the US-based cohort. The minor allele of rs201716258 was also present in Scottish ICH patients, and rs138269346 was observed in two ICH-free controls with a history of hypertension and myocardial infarction. Rs138269346 was nominally associated with non-lobar ICH risk (P=0.05), but not with lobar ICH (P=0.08), while associations between rs201716258 and ICH subtypes were non-significant (P>0.12). Both variants were considered pathogenic based on minor allele frequency ( |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://eprints.gla.ac.uk/238761/1/238761.pdf; Chung, J. et al. (2021) Rare missense functional variants at COL4A1 and COL4A2 in sporadic intracerebral hemorrhage. Neurology , 97(3), e236-e247. (doi:10.1212/WNL.0000000000012227 ) (PMID:34031201) |
| DOI: |
10.1212/WNL.0000000000012227 |
| Availability: |
https://eprints.gla.ac.uk/238761/; https://eprints.gla.ac.uk/238761/1/238761.pdf; https://doi.org/10.1212/WNL.0000000000012227 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.24F2E97B |
| Database: |
BASE |