Genetic Association of Sequence Variants Near AGER/NOTCH4 and Dementia
| Autor: | Margaret Gatz, Kaj Blennow, Andrey Alexeyenko, Chandra A. Reynolds, Anna M. Bennet, Ulrika K. Eriksson, Nancy L. Pedersen, Mun-Gwan Hong, Jonathan A. Prince |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Candidate gene Genotype Receptor for Advanced Glycation End Products Enzyme-Linked Immunosorbent Assay Locus (genetics) Human leukocyte antigen Biology Article Statistics Nonparametric PICALM Risk Factors Proto-Oncogene Proteins PSEN1 Humans Genetic Predisposition to Disease Receptors Immunologic Receptor Notch4 Gene Aged Genetic association Aged 80 and over Inflammation Genetics Receptors Notch General Neuroscience Chromosome Mapping Genetic Variation General Medicine Psychiatry and Mental health Clinical Psychology Genetic marker Case-Control Studies Chromosomes Human Pair 6 Dementia Female Geriatrics and Gerontology Genome-Wide Association Study |
| Zdroj: | Journal of Alzheimer's Disease. 24:475-484 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-2011-101848 |
| Popis: | We performed a survey of sequence variation in a series of 20 genes involved in inflammation-related pathways for association with dementia risk in twin and unrelated case-control samples consisting in total of 1462 Swedish dementia cases and 1929 controls. For a total of 218 tested genetic markers, strong evidence was obtained implicating a region near AGER and NOTCH4 on chromosome 6p with replication across both samples and maximum combined significance at marker rs1800625 (OR = 1.37, 95% CI 1.19-1.56, p = 1.36 × 10 -6 ). Imputation of the associated genomic interval provided an improved signal at rs8365, near the 3 � UTR of AGER (p = 7.34 × 10 -7 ). The associated region extends 120 kb encompassing 11 candidate genes. While AGER encodes a key receptor for amyloid- protein, an analysis of network context based upon genes now confirmed to contribute to dementia risk (AβPP, PSEN1, PSEN2, CR1, CLU, PICALM, and APOE) suggested strong functional coupling to NOTCH4, with no significant coupling to the remaining candidates. The implicated region occurs in the broad HLA locus on chromosome 6p, but associated markers were not in strong LD with known variants that regulate HLA gene function, suggesting that this may represent a signal distinct from immune-system pathways. |
| Databáze: | OpenAIRE |
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