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Association studies of 23 positional/functional candidate genes on chromosome 10 in late‐onset Alzheimer's disease
Abstract
Late‐onset Alzheimer's disease (LOAD) is a common neurodegenerative disorder, with a complex etiology. APOE is the only confirmed susceptibility gene for LOAD. Others remain yet to be found. Evidence from linkage studies suggests that a gene (or genes) conferring susceptibility for LOAD resides on chromosome 10. We studied 23 positional/functional candidate genes from our linkage region on chromosome 10 (APBB1IP, ALOX5, AD037, SLC18A3, DKK1, ZWINT, ANK3, UBE2D1, CDC2, SIRT1, JDP1, NET7, SUPV3L1, NEN3, SAR1, SGPL1, SEC24C, CAMK2G, PP3CB, SNCG, CH25H, PLCE1, ANXV111) in the MRC genetic resource for LOAD. These candidates were screened for sequence polymorphisms in a sample of 14 LOAD subjects and detected polymorphisms tested for association with LOAD in a three‐stage design involving two stages of genotyping pooled DNA samples followed by a third stage in which markers showing evidence for association in the first stages were subjected to individual genotyping. One hundred and twenty polymorphisms were identified and tested in stage 1 (4 case + 4 control pools totaling 366 case and 366 control individuals). Single nucleotide polymorphisms (SNPs) showing evidence of association with LOAD were then studied in stage 2 (8 case + 4 control pools totaling 1,001 case and 1,001 control individuals). Five SNPs, in four genes, showed evidence for association (P < 0.1) at stage 2 and were individually genotyped in the complete dataset, comprising 1,160 LOAD cases and 1,389 normal controls. Two SNPs in SGPL1 demonstrated marginal evidence of association, with uncorrected P values of 0.042 and 0.056, suggesting that variation in SGPL1 may confer susceptibility to LOAD. © 2007 Wiley‐Liss, Inc.
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“An association of CH25H with AD was first reported in a hippocampal microarray study of AD brain tissue [53] and further suggested by an AlzGene meta-analysis for a sporadic AD population [54] and other AD patient-based independent systematic analyses [55–57].”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [55]
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Self-citation25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner
Wong, M. Y., Lewis, M., Doherty, J. J., Shi, Y., Cashikar, A. G., Amelianchik, A., Tymchuk, S., Sullivan, P. M., Qian, M., Covey, D. F., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01869-3 · Cited by 121
Metadata
- Authors
- Morgan, A. R., Turic, D., Jehu, L., Hamilton, G., Hollingworth, P., Moskvina, V., Jones, L., Lovestone, S., Brayne, C., Rubinsztein, D. C., Lawlor, B., Gill, M., O'Donovan, M. C., Owen, M. J., & Williams, J.
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2007-08-20
- Volume
- 144B
- Issue
- 6
- Pages
- 762-770
- ISSN
- 1552-4841
- 1552-485X
- Cited by
- 42
- References
- 1
- Language
- en
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- Morgan, A. R., Turic, D., Jehu, L., Hamilton, G., Hollingworth, P., Moskvina, V., Jones, L., Lovestone, S., Brayne, C., Rubinsztein, D. C., Lawlor, B., Gill, M., O'Donovan, M. C., Owen, M. J., & Williams, J. (2007). Association studies of 23 positional/functional candidate genes on chromosome 10 in late‐onset Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. https://doi.org/10.1002/ajmg.b.30509