3 results on '"McCabe, Cristin"'
Search Results
2. Intersection of population variation and autoimmunity genetics in human T cell activation
- Author
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Ye, Chun Jimmie, Feng, Ting, Kwon, Ho-Keun, Raj, Towfique, Wilson, Michael T, Asinovski, Natasha, McCabe, Cristin, Lee, Michelle H, Frohlich, Irene, Paik, Hyun-il, Zaitlen, Noah, Hacohen, Nir, Stranger, Barbara, De Jager, Philip, Mathis, Diane, Regev, Aviv, and Benoist, Christophe
- Subjects
CD4-Positive T-Lymphocytes ,General Science & Technology ,Quantitative Trait Loci ,Black People ,Autoimmunity ,Lymphocyte Activation ,Autoimmune Disease ,White People ,Asian People ,Clinical Research ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Aetiology ,Whites ,Inflammatory and immune system ,Human Genome ,Genetic Variation ,Blacks ,Asians ,Gene Expression Regulation ,Multigene Family ,Cytokines ,Th17 Cells ,Genome-Wide Association Study ,Biotechnology - Abstract
T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans and its genetic or environmental roots. We analyzed gene expression in CD4(+) T cells during unbiased activation or in T helper 17 (T(H)17) conditions from 348 healthy participants representing European, Asian, and African ancestries. We observed interindividual variability, most marked for cytokine transcripts, with clear biases on the basis of ancestry, and following patterns more complex than simple T(H)1/2/17 partitions. We identified 39 genetic loci specifically associated in cis with activated gene expression. We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated IL2RA gene, affecting its activity in activated but not regulatory T cells. Thus, interindividual variability affects the fundamental immunologic process of T helper activation, with important connections to autoimmune disease.
- Published
- 2014
3. Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci
- Author
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Srivastava, Gyan, Lunnon, Katie, Burgess, Jeremy, Yu, Lei, Ernst, Jason, McCabe, Cristin, Tang, Anna, Raj, Towfique, Replogle, Joseph, Brodeur, Wendy, Gabriel, Stacey, Younkin, Curtis, Zou, Fanggeng, Szyf, Moshe, Meissner, Alexander, Ertekin-Taner, Nilufer, Kellis, Manolis, Mill, Jonathan, De Jager, Philip L., Schalkwyk, Leonard C., Eaton, Matthew Lucas, Eaton, Matthew L., Keenan, Brendan T., Chai, High S., Younkin, Steven G., Epstein, Charles B., Schneider, Julie A., Bernstein, Bradley E., Chibnik, Lori B., Bennett, David A., Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Eaton, Matthew Lucas, Ernst, Jason, Meissner, Alexander, and Kellis, Manolis
- Subjects
Male ,Aging ,Genome-wide association study ,Neurodegenerative ,Alzheimer's Disease ,80 and over ,2.1 Biological and endogenous factors ,Psychology ,Protein Interaction Maps ,Aetiology ,Epigenomics ,Genetics ,Aged, 80 and over ,General Neuroscience ,Intracellular Signaling Peptides and Proteins ,Brain ,Adaptor Proteins ,Nuclear Proteins ,Methylation ,Amyloidosis ,Middle Aged ,3. Good health ,CpG site ,Neurological ,DNA methylation ,Female ,Cognitive Sciences ,Alzheimer's disease ,Ankyrins ,and over ,Biology ,Article ,Alzheimer Disease ,Acquired Cognitive Impairment ,medicine ,Humans ,Genetic Predisposition to Disease ,Gene ,Adaptor Proteins, Signal Transducing ,Aged ,Neurology & Neurosurgery ,Tumor Suppressor Proteins ,Human Genome ,Signal Transducing ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,DNA Methylation ,medicine.disease ,Brain Disorders ,Differentially methylated regions ,Dementia ,CpG Islands ,Carrier Proteins ,Genome-Wide Association Study - Abstract
We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network., National Institutes of Health (U.S.) (Grant R01 AG036042), National Institutes of Health (U.S.) (Grant R01AG036836), National Institutes of Health (U.S.) (Grant R01 AG17917), National Institutes of Health (U.S.) (Grant R01AG15819), National Institutes of Health (U.S.) (Grant R01 AG032990), National Institutes of Health (U.S.) (Grant R01 AG18023), National Institutes of Health (U.S.) (Grant RC2 AG036547), National Institutes of Health (U.S.) (Grant P30 AG10161), National Institutes of Health (U.S.) (Grant P50 AG016574), National Institutes of Health (U.S.) (Grant U01 ES017155), National Institutes of Health (U.S.) (Grant KL2 RR024151), National Institutes of Health (U.S.) (Grant K25 AG041906-01)
- Published
- 2014
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