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- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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- Burholt, Vanessa, et al.
(author)
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Reliability and Validity of the Older Americans Resources and Services (OARS) Social Resources Scale in six European Countries
- 2007
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X. ; 62B:6, s. 371-379
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Journal article (peer-reviewed)abstract
- OBJECTIVE: This paper documents the applicability of the Older Americans Resources and Services (OARS) Social Resources Scale in six European Countries (the Netherlands, Luxembourg, Italy, Austria, the United Kingdom and Sweden). METHOD: A questionnaire was administered through face-to-face interviews in five countries, and postal interview in the sixth, to representative populations of adults aged 50-90 living independently (N=12478). The paper examines the missing values and distribution of the items in the social resources scale, and the consistency of skew and kurtosis across the countries. Item-total correlations are performed. Confirmatory factor analyses (CFA) are run to test a three factor model which was obtained in USA and Spanish analyses. Cronbach’s Alpha determines the reliability of the social resources sub-scales. RESULTS: Relatively large proportion of missing data is observed for one item (have someone who would help you). All items correlate with a score equal to or greater than 0.20. Although the CFA generally support the acceptability of the three factor structure in the European data, the reliability of two of the sub-scales (dependability and affective) is unacceptably low. DISCUSSION: Differences across countries makes it unlikely a single social resources scale can be developed that would have item equivalence in multiple countries.
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5. |
- Burholt, Vanessa, et al.
(author)
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Reliability and Validity of the Older Americans Resources and Services (OARS) Social Resources Scale in six European Countries
- 2007
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In: The journals of gerontology. Series B, Psychological sciences and social sciences. - : The Gerontological Society of America. - 1079-5014 .- 1758-5368. ; 62:6, s. 371-379
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Journal article (peer-reviewed)abstract
- Objectives. The purpose of this article is to examine data quality, reliability, and construct validity of the Older Americans Resources and Services social resources scale in six European countries (The Netherlands, Luxembourg, Italy, Austria, the United Kingdom, and Sweden).Methods. A questionnaire was administered through face-to-face interviews in five countries, and postal interview in the sixth, to representative populations of adults aged 50 to 90 living independently (N = 12,478). This article examines missing values and distribution of items in the social resources scale, and consistency of skew and kurtosis across countries. We performed item–total correlations and ran confirmatory factor analyses to test a three-factor model obtained in previous U.S. and Spanish analyses. Cronbach's alpha determined the reliability of the factors.Results. We observed a relatively large proportion of missing data for one item (have someone who would help you). All items correlated with a score equal to or greater than 0.20. Although the confirmatory factor analyses generally supported the acceptability of the three-factor structure in the European data, the reliability of two dimensions (dependability and affective) was unacceptably low.Discussion. Differences across countries make it unlikely that researchers can develop a single social resources scale that would have item equivalence in multiple countries.
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