FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2169657293> ?p ?o ?g. }

• W2169657293 endingPage "e1002237" @default.
• W2169657293 startingPage "e1002237" @default.
• W2169657293 abstract "Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df) = 10(-6), GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10(-7)) but not in light coffee-drinkers. The a priori Replication hypothesis that Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers was confirmed: OR(Replication) = 0.59, P(Replication) = 10(-3); OR(Pooled) = 0.51, P(Pooled) = 7×10(-8). Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10(-3)), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10(-13)). Imputation revealed a block of SNPs that achieved P(2df)<5×10(-8) in GWAIS, and OR = 0.41, P = 3×10(-8) in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients." @default.
• W2169657293 created "2016-06-24" @default.
• W2169657293 creator A5000226143 @default.
• W2169657293 creator A5004855604 @default.
• W2169657293 creator A5006085107 @default.
• W2169657293 creator A5010092165 @default.
• W2169657293 creator A5011961838 @default.
• W2169657293 creator A5019633865 @default.
• W2169657293 creator A5021215061 @default.
• W2169657293 creator A5032427809 @default.
• W2169657293 creator A5032614954 @default.
• W2169657293 creator A5032657027 @default.
• W2169657293 creator A5033521896 @default.
• W2169657293 creator A5034767660 @default.
• W2169657293 creator A5035009621 @default.
• W2169657293 creator A5037361988 @default.
• W2169657293 creator A5038087481 @default.
• W2169657293 creator A5051577475 @default.
• W2169657293 creator A5054911069 @default.
• W2169657293 creator A5055969440 @default.
• W2169657293 creator A5056263027 @default.
• W2169657293 creator A5059566273 @default.
• W2169657293 creator A5064427042 @default.
• W2169657293 creator A5077871707 @default.
• W2169657293 creator A5078092011 @default.
• W2169657293 creator A5079709773 @default.
• W2169657293 creator A5080323879 @default.
• W2169657293 creator A5087762989 @default.
• W2169657293 creator A5088753130 @default.
• W2169657293 date "2011-08-18" @default.
• W2169657293 modified "2023-10-07" @default.
• W2169657293 title "Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee" @default.
• W2169657293 cites W1561072761 @default.
• W2169657293 cites W1967542661 @default.
• W2169657293 cites W1967551953 @default.
• W2169657293 cites W1971999279 @default.
• W2169657293 cites W1973845468 @default.
• W2169657293 cites W1978647688 @default.
• W2169657293 cites W1979659124 @default.
• W2169657293 cites W1980991473 @default.
• W2169657293 cites W1992436001 @default.
• W2169657293 cites W1994636027 @default.
• W2169657293 cites W1998342470 @default.
• W2169657293 cites W2001785134 @default.
• W2169657293 cites W2018907079 @default.
• W2169657293 cites W2019038353 @default.
• W2169657293 cites W2019152017 @default.
• W2169657293 cites W2020219354 @default.
• W2169657293 cites W2022426651 @default.
• W2169657293 cites W2023572125 @default.
• W2169657293 cites W2028197440 @default.
• W2169657293 cites W2029107495 @default.
• W2169657293 cites W2046173010 @default.
• W2169657293 cites W2047565527 @default.
• W2169657293 cites W2051691242 @default.
• W2169657293 cites W2053969387 @default.
• W2169657293 cites W2058673913 @default.
• W2169657293 cites W2061854901 @default.
• W2169657293 cites W2063289286 @default.
• W2169657293 cites W2074652483 @default.
• W2169657293 cites W2085676043 @default.
• W2169657293 cites W2088277236 @default.
• W2169657293 cites W2093453252 @default.
• W2169657293 cites W2093977564 @default.
• W2169657293 cites W2094037121 @default.
• W2169657293 cites W2098943613 @default.
• W2169657293 cites W2099016813 @default.
• W2169657293 cites W2102304447 @default.
• W2169657293 cites W2111301888 @default.
• W2169657293 cites W2126086474 @default.
• W2169657293 cites W21310257 @default.
• W2169657293 cites W2133781643 @default.
• W2169657293 cites W2148641246 @default.
• W2169657293 cites W2149681218 @default.
• W2169657293 cites W2150107846 @default.
• W2169657293 cites W2151513507 @default.
• W2169657293 cites W2161633633 @default.
• W2169657293 cites W2162530578 @default.
• W2169657293 cites W2164683872 @default.
• W2169657293 cites W2165465283 @default.
• W2169657293 cites W2167157822 @default.
• W2169657293 cites W4296025734 @default.
• W2169657293 doi "https://doi.org/10.1371/journal.pgen.1002237" @default.
• W2169657293 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3158052" @default.
• W2169657293 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21876681" @default.
• W2169657293 hasPublicationYear "2011" @default.
• W2169657293 type Work @default.
• W2169657293 sameAs 2169657293 @default.
• W2169657293 citedByCount "200" @default.
• W2169657293 countsByYear W21696572932012 @default.
• W2169657293 countsByYear W21696572932013 @default.
• W2169657293 countsByYear W21696572932014 @default.
• W2169657293 countsByYear W21696572932015 @default.
• W2169657293 countsByYear W21696572932016 @default.
• W2169657293 countsByYear W21696572932017 @default.
• W2169657293 countsByYear W21696572932018 @default.
• W2169657293 countsByYear W21696572932019 @default.
• W2169657293 countsByYear W21696572932020 @default.

• next