% 0期刊文章%一个剑黄% Bowen苏%城镇Karhunen Verena Zuber % Dipender吉尔% % Ari Ahola-Olli % Saranya Palaniswamy % Juha奥维宁的%受到一个卡尔赫齐格% Sirkka Keinanen-Kiukaanniemi % Marko Salmi % Sirpa Jalkanen % Terho Lehtimaki % Veikko Salomaa %奥利·T·Raitakari %保罗·m·马修斯%一个保罗·艾略特% Konstantinos k . Tsilidis % Marjo-riitta Jarvelin %一个Ioanna Tzoulaki %阿巴斯Dehghan % T炎性疾病,炎症生物标记,阿尔茨海默病% B观测分析和孟德尔随机化% D R 10.1212 / WNL 2023%。0000000000201489 % J首页神经病学% P e568-e581 % V 100% N 6% X背景和目标是否慢性自身免疫性炎症疾病会影响阿尔茨海默病(AD)的风险是有争议的。我们为炎性疾病之间的关系和风险的广告和探索循环炎症生物标记的作用在炎性疾病和广告之间的关系。方法我们进行观察分析慢性自身免疫性炎症性疾病和广告的风险,使用的数据来自2047513名参与者中确定英国临床实践研究数据链接(CPRD)。使用数据共有超过1100000人从15个大型全基因组关联研究的数据集,我们执行2-sample孟德尔随机化(夫人)调查慢性自身免疫性炎症疾病之间的关系,循环炎症生物标志物的水平,和广告的风险。结果Cox回归模型使用CPRD数据显示广告的总体发病率较高患者炎症性肠病(危险比[HR] 1.17;95%可信区间1.15 - -1.19;p = 2.1×10−4),其他炎症polyarthropathies和系统化的结缔组织疾病(HR 1.13;95%可信区间1.12 - -1.14;p = 8.6×10−5),牛皮癣(HR 1.13;95%可信区间1.10 - -1.16;p = 2.6×10−4),类风湿性关节炎(HR 1.08; 95% CI 1.06–1.11; p = 4.0 × 10−4), and multiple sclerosis (HR 1.06; 95% CI 1.04–1.07; p = 2.8 × 10−4) compared with the age (±5 years) and sex-matched comparison groups free from all inflammatory diseases under investigation. Bidirectional MR analysis identified relationships between chronic autoimmune inflammatory diseases and circulating inflammatory biomarkers. Particularly, circulating monokine induced by gamma interferon (MIG) level was suggestively associated with a higher risk of AD (odds ratio from inverse variance weighted [ORIVW] 1.23; 95% CI 1.06–1.42; pIVW = 0.007) and lower risk of Crohn disease (ORIVW 0.73; 95% CI −0.62 to 0.86; pIVW = 1.3 × 10−4). Colocalization supported a common causal single nucleotide polymorphism for MIG and Crohn disease (posterior probability = 0.74), but not AD (posterior probability = 0.03). Using a 2-sample MR approach, genetically predicted risks of inflammatory diseases were not associated with higher AD risk.Discussion Our data suggest that the association between inflammatory diseases and risk of AD is unlikely to be causal and may be a result of confounding. In support, although inflammatory biomarkers showed evidence for causal associations with inflammatory diseases, evidence was weak that they affected both inflammatory disease and AD.Aβ=β-amyloid; AD=Alzheimer disease; BMI=body mass index; CIF=cumulative incidence function; CPRD=Clinical Practice Research Datalink; EHR=electronic health record; GP=general practitioner; GWAS=genome-wide association study; HES=Hospital Episode Statistics; HR=hazard ratio; IBD=inflammatory bowel disease; IGAP=International Genomics of Alzheimer's Project; IL=interleukin; IMD=index of multiple deprivation; IPTW=inverse propensity score treatment weighting; IVW=inverse-variance weighting; MIG=monokine induced by gamma interferon; MR=Mendelian randomization; MS=multiple sclerosis; OID=other inflammatory polyarthropathies and systematic connective tissue disorders; ONS=Office of National Statistics; OR=odds ratio; PP.H4=posterior probability; RA=rheumatoid arthritis; SNP=single nucleotide polymorphism; UC=ulcerative colitis %U //www.ez-admanager.com/content/neurology/100/6/e568.full.pdf