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- Manzoni, Claudia, et al.
(författare)
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Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
- 2024
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
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| 2. |
- Tayefi, Maryam, et al.
(författare)
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Challenges and opportunities beyond structured data in analysis of electronic health records
- 2021
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Ingår i: Wiley Interdisciplinary Reviews. - : Wiley. - 1939-5108 .- 1939-0068. ; 13:6
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Forskningsöversikt (refereegranskat)abstract
- Electronic health records (EHR) contain a lot of valuable information about individual patients and the whole population. Besides structured data, unstructured data in EHRs can provide extra, valuable information but the analytics processes are complex, time-consuming, and often require excessive manual effort. Among unstructured data, clinical text and images are the two most popular and important sources of information. Advanced statistical algorithms in natural language processing, machine learning, deep learning, and radiomics have increasingly been used for analyzing clinical text and images. Although there exist many challenges that have not been fully addressed, which can hinder the use of unstructured data, there are clear opportunities for well-designed diagnosis and decision support tools that efficiently incorporate both structured and unstructured data for extracting useful information and provide better outcomes. However, access to clinical data is still very restricted due to data sensitivity and ethical issues. Data quality is also an important challenge in which methods for improving data completeness, conformity and plausibility are needed. Further, generalizing and explaining the result of machine learning models are important problems for healthcare, and these are open challenges. A possible solution to improve data quality and accessibility of unstructured data is developing machine learning methods that can generate clinically relevant synthetic data, and accelerating further research on privacy preserving techniques such as deidentification and pseudonymization of clinical text.
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