2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T777,Elevated antimicrobial antibodies have been reported up to 6 years before diagnosis of Crohn's disease (CD), but the specific antibody response is unclear. Here, we characterized the antimicrobial antibody responses before CD diagnosis in healthy first-degree relatives (FDR) of CD patients. The CCC-GEM (Crohn's and Colitis Canada - Genetic, Environmental, Microbial) Project nested case-control cohort consisted of FDRs who later developed CD (N = 77), matched 1:4 by age, sex, follow-up duration, and geographical location with healthy FDRs (N = 304). Sera at enrollment were probed for antimicrobial reactivity using a microbiota antigen microarray and a flagellin peptide cytometric bead array. Conditional logistic regression was used to assess association with CD onset; and partial Spearman was used to correlate serologic responses with lactulose-to-mannitol ratio (LMR), C-reactive protein (CRP) and fecal calprotectin (FCP). False discovery rate was controlled using the Benjamini-Hochberg method (q < 0.05). 19 out of 49 IgG antimicrobial antibody responses were significantly associated with the risk of CD; these antibodies were reactive to Lachnospiraceae family, particularly Roseburia-derived flagellins; 5 antibodies positively correlated with FCP, whereas 3 positively correlated with LMR. These IgG-seroreactive flagellins shared significant amino acid sequence homology, characterized by a conserved "hinge peptide" within D0-D1 domains of the amino-terminus. The cytometric bead array confirmed that elevated IgG seroreactivity to the hinge peptide is associated with future risk of CD independent of LMR and FCP. Increased antibody response in healthy FDRs towards Lachnospiraceae flagellins is associated with future risk of CD. Importantly, pre-CD subjects shared seroreactivity towards a conserved bacterial flagellin epitope, which may represent an early pre-clinical biomarker of CD.31:T449,A total of 81 713 cases of SA (50 512 [61.8%] female; mean [SD] age, 32.3 [14.9] years), with 408 490 age-matched controls (252 525 [61.8%] female; mean [SD] age, 32.3 [14.9] years), and 9362 cases of suicide (2360 [25.2%] female; mean [SD] age, 45.1 [14.6] years), along with 46 749 matched controls (11 796 [25.2%] female; mean [SD] age, 45.1 [14.6] years) who were alive at the date of the case's death, were included in the health conditions analysis. The PGS analysis included 8221 cases of SA (5944 [72.3%] female; mean [SD] age, 19.7 [4.4] years) and 225 cases of suicide (80 [35.6%] female; mean [SD] age, 24.6 [5.0] years). Chronic diseases (eg, dyslipidemia or hearing problems) showed stronger associations with SA, while severe conditions (eg, cancer) were more strongly associated with suicide. Suicide was influenced only by PGSs for mental disorders, whereas SA was associated with both psychiatric and broader health-related genetic risk factors. Notably, dose-response associations were observed for most health conditions and PGSs in relation to cumulative SA burden.32:Ta95,Not all individuals who die by suicide have a history of nonfatal suicide attempt (SA); however, little is known about the extent to which the genetic and environmental etiologies of SA and suicide are shared or distinct. To examine shared and distinct risk factors for SA and suicide, focusing on clinically diagnosed health conditions and genetic factors. For health conditions, a nested case-control study was performed using data from the Danish registers. For genetic factors, a case-control analysis framework was used, with individual genotypes retrieved from the iPSYCH2015 dataset, which was nested within the entire Danish population. Individuals older than 10 years were included to minimize the risk of misclassification for SA and suicide. Data were analyzed from January 2024 to April 2025. Twenty-eight health conditions and 35 polygenic scores (PGSs) for complex traits. The primary outcomes were SA, suicide, and cumulative SA burden. Associations between health conditions and the risk of SA and suicide were assessed using conditional logistic regression. PGSs for complex traits were calculated using LDpred2-auto, and their associations with SA and suicide were evaluated via logistic regression. To assess whether effect sizes differed significantly between SA and suicide, bayesian model-based classification and Cochran Q test were applied. A total of 81 713 cases of SA (50 512 [61.8%] female; mean [SD] age, 32.3 [14.9] years), with 408 490 age-matched controls (252 525 [61.8%] female; mean [SD] age, 32.3 [14.9] years), and 9362 cases of suicide (2360 [25.2%] female; mean [SD] age, 45.1 [14.6] years), along with 46 749 matched controls (11 796 [25.2%] female; mean [SD] age, 45.1 [14.6] years) who were alive at the date of the case's death, were included in the health conditions analysis. The PGS analysis included 8221 cases of SA (5944 [72.3%] female; mean [SD] age, 19.7 [4.4] years) and 225 cases of suicide (80 [35.6%] female; mean [SD] age, 24.6 [5.0] years). Chronic diseases (eg, dyslipidemia or hearing problems) showed stronger associations with SA, while severe conditions (eg, cancer) were more strongly associated with suicide. Suicide was influenced only by PGSs for mental disorders, whereas SA was associated with both psychiatric and broader health-related genetic risk factors. Notably, dose-response associations were observed for most health conditions and PGSs in relation to cumulative SA burden. A broad range of health conditions and genetic factors were associated with increased risk of both outcomes; however, their shared and distinct risk factors suggest that SA and death by suicide are not solely differentiated by liability severity.33:Tfeb, Importance Not all individuals who die by suicide have a history of nonfatal suicide attempt (SA); however, little is known about the extent to which the genetic and environmental etiologies of SA and suicide are shared or distinct. Objective To examine shared and distinct risk factors for SA and suicide, focusing on clinically diagnosed health conditions and genetic factors. Design, Setting, and Participants For health conditions, a nested case-control study was performed using data from the Danish registers. For genetic factors, a case-control analysis framework was used, with individual genotypes retrieved from the iPSYCH2015 dataset, which was nested within the entire Danish population. Individuals older than 10 years were included to minimize the risk of misclassification for SA and suicide. Data were analyzed from January 2024 to April 2025. Exposures Twenty-eight health conditions and 35 polygenic scores (PGSs) for complex traits. Main Outcomes and Measures The primary outcomes were SA, suicide, and cumulative SA burden. Associations between health conditions and the risk of SA and suicide were assessed using conditional logistic regression. PGSs for complex traits were calculated using LDpred2-auto, and their associations with SA and suicide were evaluated via logistic regression. To assess whether effect sizes differed significantly between SA and suicide, bayesian model-based classification and Cochran Q test were applied. Results A total of 81 713 cases of SA (50 512 [61.8%] female; mean [SD] age, 32.3 [14.9] years), with 408 490 age-matched controls (252 525 [61.8%] female; mean [SD] age, 32.3 [14.9] years), and 9362 cases of suicide (2360 [25.2%] female; mean [SD] age, 45.1 [14.6] years), along with 46 749 matched controls (11 796 [25.2%] female; mean [SD] age, 45.1 [14.6] years) who were alive at the date of the case’s death, were included in the health conditions analysis. The PGS analysis included 8221 cases of SA (5944 [72.3%] female; mean [SD] age, 19.7 [4.4] years) and 225 cases of suicide (80 [35.6%] female; mean [SD] age, 24.6 [5.0] years). Chronic diseases (eg, dyslipidemia or hearing problems) showed stronger associations with SA, while severe conditions (eg, cancer) were more strongly associated with suicide. Suicide was influenced only by PGSs for mental disorders, whereas SA was associated with both psychiatric and broader health-related genetic risk factors. Notably, dose-response associations were observed for most health conditions and PGSs in relation to cumulative SA burden. Conclusions and Relevance A broad range of health conditions and genetic factors were associated with increased risk of both outcomes; however, their shared and distinct risk factors suggest that SA and death by suicide are not solely differentiated by liability severity. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Nested Case-Control: study design Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Nested Case-Control (study design). Clinician-written summaries and actionable practice insights. 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These IgG-seroreactive flagellins shared significant amino acid sequence homology, characterized by a conserved \"hinge peptide\" within D0-D1 domains of the amino-terminus. The cytometric bead array confirmed that elevated IgG seroreactivity to the hinge peptide is associated with future risk of CD independent of LMR and FCP.","abstract":"$30","keywords":["Anti-flagellin Antibody","Crohn’s Disease","Pre-disease","Serology"],"pubmed_id":"41534761","conclusions":"Increased antibody response in healthy FDRs towards Lachnospiraceae flagellins is associated with future risk of CD. Importantly, pre-CD subjects shared seroreactivity towards a conserved bacterial flagellin epitope, which may represent an early pre-clinical biomarker of CD.","publication_date":"2026-01-15T00:00:00"},"crossref":{"DOI":"10.1016/j.cgh.2025.12.006","URL":"https://doi.org/10.1016/j.cgh.2025.12.006","ISSN":["1542-3565"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S1542356525010316?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S1542356525010316?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Serum IgG Response to a Conserved Domain of Commensal Flagellins Predicts Future Risk of Crohn’s Disease in First-degree Relatives"],"author":[{"given":"Richard Y.","family":"Wu","sequence":"first","affiliation":[]},{"given":"Mingyue","family":"Xue","sequence":"additional","affiliation":[]},{"given":"Qing","family":"Zhao","sequence":"additional","affiliation":[]},{"given":"Sean","family":"Jeong","sequence":"additional","affiliation":[]},{"given":"Anne M.","family":"Griffiths","sequence":"additional","affiliation":[]},{"given":"Levinus A.","family":"Dieleman","sequence":"additional","affiliation":[]},{"given":"A. 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The health-condition analysis included 81,713 suicide attempt cases with 408,490 controls and 9,362 suicide cases with 46,749 controls; the genetic analysis included 8,221 attempt cases and 225 suicide cases.","key_result":"Chronic diseases (e.g., dyslipidemia, hearing problems) showed stronger associations with suicide attempt, while severe conditions (e.g., cancer) were more strongly associated with suicide. Suicide related only to polygenic scores for mental disorders, whereas attempts related to both psychiatric and broader health-related genetic risk; dose-response patterns were observed for most health conditions and polygenic scores with cumulative attempt burden.","practice_takeaway":"Do not equate suicide attempt and suicide as the same risk state: chronic diseases tracked more with attempts, while severe illnesses like cancer tracked more with suicide in this Danish analysis. 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