id:"swepub:oai:prod.swepub.kib.ki.se:149838640"
Search: id:"swepub:oai:prod.swepub.kib.ki.se:149838640" > A Genetic Associati...
- 1 of 1
- Previous record
- Next record
- To hitlist
- Haessler, S (author)
A Genetic Association Test Accounting for Skewed X-Inactivation With Application to Biotherapy Immunogenicity in Patients With Autoimmune Diseases
- Article/chapterEnglish2022
Publisher, publication year, extent ...
- 2022-06-01
- Frontiers Media SA,2022
Numbers
- LIBRIS-ID:oai:prod.swepub.kib.ki.se:149838640
- http://kipublications.ki.se/Default.aspx?queryparsed=id:149838640URI
- https://doi.org/10.3389/fmed.2022.856917DOI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- Despite being assayed on commercialized DNA chips, the X chromosome is commonly excluded from genome-wide association studies (GWAS). One of the reasons is the complexity to analyze the data taking into account the X-chromosome inactivation (XCI) process in women and in particular the XCI process with a potentially skewed pattern. This is the case when investigating the role of X-linked genetic variants in the occurrence of anti-drug antibodies (ADAs) in patients with autoimmune diseases treated by biotherapies. In this context, we propose a novel test statistic for selecting loci of interest harbored by the X chromosome that are associated with time-to-event data taking into account skewed X-inactivation (XCI-S). The proposed statistic relies on a semi-parametric additive hazard model and is straightforward to implement. Results from the simulation study show that the test provides higher power gains than the score tests from the Cox model (under XCI process or its escape) and the Xu et al.'s XCI-S likelihood ratio test. We applied the test to the data from the real-world observational multicohort study set-up by the IMI-funded ABIRISK consortium for identifying X chromosome susceptibility loci for drug immunogenicity in patients with autoimmune diseases treated by biotherapies. The test allowed us to select two single nucleotide polymorphisms (SNPs) with high linkage disequilibrium (rs5991366 and rs5991394) located in the cytoband Xp22.2 that would have been overlooked by the Cox score tests and the Xu et al.'s XCI-S likelihood ratio test. Both SNPs showed a similar protective effect for drug immunogenicity without any occurrence of ADA positivity for the homozygous females and hemizygous males for the alternative allele. To our knowledge, this is the first study to investigate the association between X chromosome loci and the occurrence of anti-drug antibodies. We think that more X-Chromosome GWAS should be performed and that the test is well-suited for identifying X-Chromosome SNPs, while taking into account all patterns of the skewed X-Chromosome inactivation process.
Added entries (persons, corporate bodies, meetings, titles ...)
- Camilleri-Broet, S (author)
- Allez, M (author)
- Deisenhammer, F (author)
- Fogdell-Hahn, AKarolinska Institutet (author)
- Mariette, X (author)
- Pallardy, M (author)
- Broet, P (author)
- Karolinska Institutet (creator_code:org_t)
Related titles
- In:Frontiers in medicine: Frontiers Media SA9, s. 856917-2296-858X
Internet link
Find in a library
- Frontiers in medicine (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Haessler, S
- Camilleri-Broet, ...
- Allez, M
- Deisenhammer, F
- Fogdell-Hahn, A
- Mariette, X
- show more...
- Pallardy, M
- Broet, P
- show less...
- Articles in the publication
- Frontiers in med ...
- By the university
- Karolinska Institutet
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
