- Title
- Ensemble machine learning identifies genetic loci associated with future worsening of disability in people with multiple sclerosis
- Creator
- Fuh-Ngwa, Valery; Zhou, Yuan; Melton, Phillip E.; van der Mei, Ingrid; Charlesworth, Jac C.; Lin, Xin; Zarghami, Amin; Broadley, Simon A.; Ponsonby, Anne-Louise; Simpson-Yap, Steve; Lechner-Scott, Jeannette; Taylor, Bruce V.
- Relation
- Scientific Reports Vol. 12, no. 19291
- Publisher Link
- http://dx.doi.org/10.1038/s41598-022-23685-w
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2022
- Description
- Limited studies have been conducted to identify and validate multiple sclerosis (MS) genetic loci associated with disability progression. We aimed to identify MS genetic loci associated with worsening of disability over time, and to develop and validate ensemble genetic learning model(s) to identify people with MS (PwMS) at risk of future worsening. We examined associations of 208 previously established MS genetic loci with the risk of worsening of disability; we learned ensemble genetic decision rules and validated the predictions in an external dataset. We found 7 genetic loci (rs7731626: HR 0.92, P = 2.4 × 10–5; rs12211604: HR 1.16, P = 3.2 x 10–7; rs55858457: HR 0.93, P = 3.7 x 10–7; rs10271373: HR 0.90, P = 1.1 x 10–7; rs11256593: HR 1.13, P = 5.1 x 10–57; rs12588969: HR = 1.10, P = 2.1 x 10–10; rs1465697: HR 1.09, P = 1.7 x 10–128) associated with risk worsening of disability; most of which were located near or tagged to 13 genomic regions enriched in peptide hormones and steroids biosynthesis pathways by positional and eQTL mapping. The derived ensembles produced a set of genetic decision rules that can be translated to provide additional prognostic values to existing clinical predictions, with the additional benefit of incorporating relevant genetic information into clinical decision making for PwMS. The present study extends our knowledge of MS progression genetics and provides the basis of future studies regarding the functional significance of the identified loci.
- Subject
- multiple sclerosis (MS); genetic loci; disability; future worsening
- Identifier
- http://hdl.handle.net/1959.13/1488201
- Identifier
- uon:52379
- Identifier
- ISSN:2045-2322
- Rights
- Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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