ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for risk out of >500 occurrences
421954 occurrences (No.40 in the rank) during 5 years in the PubMed. [cache]
367) Here, we describe a deep post-GWAS analysis of AD-associated variants, using an integrated computational framework for predicting both disease genes and their risk variants.
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PMID:34654853 DOI:10.1038/s41598-021-99352-3
2021 Scientific reports
* Deep post-GWAS analysis identifies potential risk genes and risk variants for Alzheimer's disease, providing new insights into its disease mechanisms.
- Alzheimer's disease (AD) is a genetically complex, multifactorial neurodegenerative disease. It affects more than 45 million people worldwide and currently remains untreatable. Although genome-wide association studies (GWAS) have identified many AD-associated common variants, only about 25 genes are currently known to affect the risk of developing AD, despite its highly polygenic nature. Moreover, the risk variants underlying GWAS AD-association signals remain unknown. Here, we describe a deep post-GWAS analysis of AD-associated variants, using an integrated computational framework for predicting both disease genes and their risk variants. We identified 342 putative AD risk genes in 203 risk regions spanning 502 AD-associated common variants. 246 AD risk genes have not been identified as AD risk genes by previous GWAS collected in GWAS catalogs, and 115 of 342 AD risk genes are outside the risk regions, likely under the regulation of transcriptional regulatory elements contained therein. Even more significantly, for 109 AD risk genes, we predicted 150 risk variants, of both coding and regulatory (in promoters or enhancers) types, and 85 (57%) of them are supported by functional annotation. In-depth functional analyses showed that AD risk genes were overrepresented in AD-related pathways or GO terms-e.g., the complement and coagulation cascade and phosphorylation and activation of immune response-and their expression was relatively enriched in microglia, endothelia, and pericytes of the human brain. We found nine AD risk genes-e.g., IL1RAP, PMAIP1, LAMTOR4-as predictors for the prognosis of AD survival and genes such as ARL6IP5 with altered network connectivity between AD patients and normal individuals involved in AD progression. Our findings open new strategies for developing therapeutics targeting AD risk genes or risk variants to influence AD pathogenesis.
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[frequency of next (right) word to risk]
(1)139 of (11)7 prediction (21)3 decision (31)2 markers
(2)49 factors (12)6 stratification (22)3 or (32)2 mitigation
(3)46 for (13)5 individuals (23)3 patients (33)2 population
(4)21 *null* (14)4 genes (24)2 (OR (34)2 ratio
(5)19 factor (15)4 populations (25)2 among (35)2 reduction
(6)16 and (16)4 score (26)2 communication (36)2 screening
(7)13 assessment (17)4 to (27)2 communication, (37)2 strategies
(8)12 in (18)4 variants (28)2 designations
(9)8 perception (19)3 alleles (29)2 group
(10)7 factors, (20)3 assessment, (30)2 is

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--- WordNet output for risk --- =>1.損害の恐れ, 危険, 冒険, リスク, 2.危険にさらす, 3.敢えてする, 被保険者, 被保険物, 危険にさらす, 賭けてみる Overview of noun risk The noun risk has 4 senses (first 2 from tagged texts) 1. (4) hazard, jeopardy, peril, risk, endangerment -- (a source of danger; a possibility of incurring loss or misfortune; "drinking alcohol is a health hazard") 2. (2) risk, peril, danger -- (a venture undertaken without regard to possible loss or injury; "he saw the rewards but not the risks of crime"; "there was a danger he would do the wrong thing") 3. risk, risk of infection -- (the probability of becoming infected given that exposure to an infectious agent has occurred) 4. risk, risk of exposure -- (the probability of being exposed to an infectious agent) Overview of verb risk The verb risk has 2 senses (first 2 from tagged texts) 1. (8) risk, put on the line, lay on the line -- (expose to a chance of loss or damage; "We risked losing a lot of money in this venture"; "Why risk your life?"; "She laid her job on the line when she told the boss that he was wrong") 2. (2) gamble, chance, risk, hazard, take chances, adventure, run a risk, take a chance -- (take a risk in the hope of a favorable outcome; "When you buy these stocks you are gambling") --- WordNet end ---