FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3133996942> ?p ?o ?g. }

• W3133996942 abstract "Background: PLCG2 plays an important role in immune system signaling, and is expressed in several immune cell types including microglia in the brain. In 2017, the genetic variant rs72824905 (p.Pro522Arg) in the PLCG2 gene (Phospholipase C Gamma 2) was associated with a reduced risk of Alzheimer's disease (AD). Here we investigated whether the rs72824905 variant had a similar protective effect on six other brain diseases. We further tested if rs72824905 increases the likelihood of longevity, since a reduced risk of neurodegenerative diseases might associate with general survival. Methods:  We investigated the effect of carrying rs72824905 on disease risk in a total of 53,627 patients with one of seven brain diseases. We studied AD (N = 4,985), frontotemporal dementia (FTD) (N = 2,437), dementia with Lewy-bodies (DLB) (N = 1,446), progressive supranuclear palsy (PSP) (N = 882), Parkinson's disease (PD) (N = 28,448) amyotrophic lateral sclerosis (ALS) (N = 10,953) and multiple sclerosis (MS) (N = 4,476) by comparing them with in total 149,290 controls using logistic regression models. Next, we studied the effect of carrying rs72824905 on longevity by comparing individuals who reached at least 90 years (N = 3,516) with individuals who died before age 90 years or were last screened before 90 years (N = 9,677). In addition, we studied the association of rs72824905 with survival after the age of 90 in a subset of long-lived individuals followed until death. Finally, we supported our findings by studying by-proxy phenotypes in the ~450.000 participants of the UK Biobank. We associated the rs72824905 genotypes of UK Biobank participants with parental history of dementia as proxy for dementia and as a proxy for longevity we studied parental age over 90 as well as parental age over 95 years of age. All individuals were of European ancestry. Results: The rs72824905-G allele associated with a reduced AD risk (Odds ratio (OR) = 0·57, p = 4·7×10-4), a reduced DLB risk (OR = 0·54, p = 4·5×10-2) and reduced FTD risk (OR = 0·61, p = 1·0×10 2). We did not find evidence for association of rs72824905 with the risks of PSP (OR = 1·46, p = 0·19), PD (OR = 1·18, p = 0·10), ALS (OR = 1·07, p = 0·26) or MS (OR = 0·99, p = 0·95). The rs72824905-G allele was associated with a 1·49 increased likelihood of reaching >90 years (p = 6.4×10-3): variant carriers lived longer after the age of 90 years, median 4.7 (inter quartile range = 1·9 - 7·4) years compared to non-carriers 3.3 (IQR = 1·4 - 5·8) (Hazard ratio = 0·75, p = 0·07). By-proxy analyses supported the associations of rs728824905 with dementia as well as longevity. Variant carriers had a lower likelihood of having a parent with dementia (OR = 0·88, p = 1·8×10 3) and had a significantly increased likelihood of having a parent aged >95 years (OR = 1·19, p = 2·1×10-2). Conclusions: Our results show that rs72824905 in PLCG2 protects from AD, DLB and FTD and increases the likelihood of longevity. Together, our findings highlight a central role for PLCG2 related immune signaling in the brain, which should be the subject of future studies as a drug target for multiple brain diseases.   Funding Statement: The authors present a short description of 16 cohorts, often including multiple sites or studies, that contributed to this manuscript and their funding sources in Supplementary Table 1: Amsterdam dementia Cohort (ADC), 100-Plus study, German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe), Brain compendium, Clinical AD, Sweden, Danish data, Fundacio ACE (FACE), Genetics of Healthy Ageing Study (GEHA – NL), Gothenburg Birth Cohort (GBC) Studies, International FTD-Genomics Consortium (IFGC), Kompetenznetz Multiple Sklerose (KKNMS), Longitudinal Aging Study Amsterdam (LASA), Leiden Longevity Study, Maria Carolina Dalmasso, Mayo Clinic AD, DLB, PD, PSP, NDRU cohort, Oviedo, Pascual Sanchez-Juan, Project MinE, Risk and modifying factors in Fronto Temporal Dementia (RiMoD-FTD): follows The SPIN cohort, San Sebastian, UK Biobank analysis, IPDGC (The International Parkinson Disease Genomics Consortium).Declaration of Interests: The authors declare no competing interest related to this work.Ethics Approval Statement: Studies were approved by corresponding ethics committees and informed consent was obtained for all participants." @default.
• W3133996942 created "2021-03-15" @default.
• W3133996942 creator A5000884161 @default.
• W3133996942 creator A5003799076 @default.
• W3133996942 creator A5004846670 @default.
• W3133996942 creator A5005051648 @default.
• W3133996942 creator A5006945543 @default.
• W3133996942 creator A5008509307 @default.
• W3133996942 creator A5008754362 @default.
• W3133996942 creator A5009044500 @default.
• W3133996942 creator A5009533777 @default.
• W3133996942 creator A5010797490 @default.
• W3133996942 creator A5011744906 @default.
• W3133996942 creator A5012378779 @default.
• W3133996942 creator A5013502498 @default.
• W3133996942 creator A5014165648 @default.
• W3133996942 creator A5015171397 @default.
• W3133996942 creator A5017000677 @default.
• W3133996942 creator A5020077464 @default.
• W3133996942 creator A5022481370 @default.
• W3133996942 creator A5022747229 @default.
• W3133996942 creator A5023015206 @default.
• W3133996942 creator A5023893355 @default.
• W3133996942 creator A5024866832 @default.
• W3133996942 creator A5025313057 @default.
• W3133996942 creator A5025866865 @default.
• W3133996942 creator A5025870220 @default.
• W3133996942 creator A5026774627 @default.
• W3133996942 creator A5027347263 @default.
• W3133996942 creator A5027884493 @default.
• W3133996942 creator A5028556756 @default.
• W3133996942 creator A5031173940 @default.
• W3133996942 creator A5031293890 @default.
• W3133996942 creator A5032286909 @default.
• W3133996942 creator A5032387052 @default.
• W3133996942 creator A5032978826 @default.
• W3133996942 creator A5033800721 @default.
• W3133996942 creator A5035872689 @default.
• W3133996942 creator A5036878959 @default.
• W3133996942 creator A5040380636 @default.
• W3133996942 creator A5041198772 @default.
• W3133996942 creator A5043377116 @default.
• W3133996942 creator A5045246745 @default.
• W3133996942 creator A5045721609 @default.
• W3133996942 creator A5046044622 @default.
• W3133996942 creator A5046814636 @default.
• W3133996942 creator A5046997994 @default.
• W3133996942 creator A5047564828 @default.
• W3133996942 creator A5048283190 @default.
• W3133996942 creator A5048291075 @default.
• W3133996942 creator A5048408999 @default.
• W3133996942 creator A5048570234 @default.
• W3133996942 creator A5049349862 @default.
• W3133996942 creator A5050897246 @default.
• W3133996942 creator A5051228144 @default.
• W3133996942 creator A5051878993 @default.
• W3133996942 creator A5052016436 @default.
• W3133996942 creator A5052699801 @default.
• W3133996942 creator A5052717361 @default.
• W3133996942 creator A5052975905 @default.
• W3133996942 creator A5054688310 @default.
• W3133996942 creator A5055558719 @default.
• W3133996942 creator A5057196521 @default.
• W3133996942 creator A5057540991 @default.
• W3133996942 creator A5057584473 @default.
• W3133996942 creator A5057719938 @default.
• W3133996942 creator A5057731725 @default.
• W3133996942 creator A5057989264 @default.
• W3133996942 creator A5058286274 @default.
• W3133996942 creator A5059027860 @default.
• W3133996942 creator A5059183048 @default.
• W3133996942 creator A5059526712 @default.
• W3133996942 creator A5062316104 @default.
• W3133996942 creator A5063552729 @default.
• W3133996942 creator A5065172118 @default.
• W3133996942 creator A5065546490 @default.
• W3133996942 creator A5065646667 @default.
• W3133996942 creator A5066197769 @default.
• W3133996942 creator A5066352714 @default.
• W3133996942 creator A5066801947 @default.
• W3133996942 creator A5069432142 @default.
• W3133996942 creator A5072178658 @default.
• W3133996942 creator A5072627174 @default.
• W3133996942 creator A5074593768 @default.
• W3133996942 creator A5074775445 @default.
• W3133996942 creator A5076348059 @default.
• W3133996942 creator A5076556785 @default.
• W3133996942 creator A5077200969 @default.
• W3133996942 creator A5077506936 @default.
• W3133996942 creator A5077545737 @default.
• W3133996942 creator A5078312670 @default.
• W3133996942 creator A5078795785 @default.
• W3133996942 creator A5079539237 @default.
• W3133996942 creator A5080705428 @default.
• W3133996942 creator A5083330654 @default.
• W3133996942 creator A5083492046 @default.
• W3133996942 creator A5084072142 @default.
• W3133996942 creator A5084980420 @default.
• W3133996942 creator A5085487257 @default.
• W3133996942 creator A5085616253 @default.

• next