کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6803663 | 1433547 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium
ترجمه فارسی عنوان
کشف تعاملات ژن-ژن در مجموعه داده های چندگانه مستقل از بیماری آلزایمر مبتلا به آلزایمر از کنسرسیوم ژنتیک آلزایمر
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
چکیده انگلیسی
Late-onset Alzheimer disease (AD) has a complex genetic etiology, involving locus heterogeneity, polygenic inheritance, and gene-gene interactions; however, the investigation of interactions in recent genome-wide association studies has been limited. We used a biological knowledge-driven approach to evaluate gene-gene interactions for consistency across 13 data sets from the Alzheimer Disease Genetics Consortium. Fifteen single nucleotide polymorphism (SNP)-SNP pairs within 3 gene-gene combinations were identified: SIRT1Â Ã ABCB1, PSAPÂ Ã PEBP4, and GRIN2BÂ Ã ADRA1A. In addition, we extend a previously identified interaction from an endophenotype analysis between RYR3Â Ã CACNA1C. Finally, post hoc gene expression analyses of the implicated SNPs further implicate SIRT1 and ABCB1, and implicate CDH23 which was most recently identified as an AD risk locus in an epigenetic analysis of AD. The observed interactions in this article highlight ways in which genotypic variation related to disease may depend on the genetic context in which it occurs. Further, our results highlight the utility of evaluating genetic interactions to explain additional variance in AD risk and identify novel molecular mechanisms of AD pathogenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 38, February 2016, Pages 141-150
Journal: Neurobiology of Aging - Volume 38, February 2016, Pages 141-150
نویسندگان
Timothy J. Hohman, William S. Bush, Lan Jiang, Kristin D. Brown-Gentry, Eric S. Torstenson, Scott M. Dudek, Shubhabrata Mukherjee, Adam Naj, Brian W. Kunkle, Marylyn D. Ritchie, Eden R. Martin, Gerard D. Schellenberg, Richard Mayeux, Lindsay A. Farrer,