Background & Aims: Oxidative stress is an essential factor in the pathogenesis of inflammatory bowel disease (IBD). A previous study found protective potential of some antioxidative nutrients against IBD. However, the association between total antioxidant capacity (TAC) of the diet and incident IBD is unclear.
Methods: We conducted a prospective cohort study including 186,195 IBD-free participants at baseline from the UK Biobank. We calculated dietary TAC using the oxygen radical absorbance capacity method based on repeated online 24-hour dietary recalls. Crohn's disease (CD) and ulcerative colitis (UC) were identified via inpatient register and primary care data. Genetic susceptibility for IBD was assessed by a polygenic risk score. Cox proportional hazard models were applied to estimate multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).
Results: During a median follow-up of 11.4 years, we identified 396 CD and 809 UC incident cases. Individuals with the highest quintile of dietary TAC had a lower risk of CD (27.0 vs 17.0 cases/100,000 person-years; aHR, 0.66; 95% CI, 0.49-0.90) but not UC (46.7 vs 35.5 cases/100,000 person-years; aHR, 0.85; 95% CI, 0.69-1.06) compared with the lowest group. We observed interactions between TAC and genetic susceptibility at both multiplicative (P-interaction = .008/0.063 for CD/UC) and additive (both P values > 1) scales. Additionally, a polymorphism of the endogenous antioxidant enzyme gene SOD2 (rs4880) modified the dietary TAC-UC association (P-interaction = .039).
Conclusion: This study suggests that a diet with high TAC may help prevent the development of IBD, particularly in individuals at high genetic risk of IBD and in mutation carriers of rs4880 in SOD2.
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http://dx.doi.org/10.1016/j.cgh.2024.09.033 | DOI Listing |
Alzheimers Dement
December 2024
Huashan Hospital, Fudan University, Shanghai, Shanghai, China.
Background: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology, yet most known loci were only identified from the late-onset type of European ancestry.
Method: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6,878 Chinese and 487,511 European individuals.
Result: We demonstrated a shared genetic architecture between early- and late-onset AD.
Geroscience
January 2025
Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Erwin Mill Building, 2024 W. Main St, Durham, NC, 27705, USA.
Genetics is the second strongest risk factor for Alzheimer's disease (AD) after age. More than 70 loci have been implicated in AD susceptibility so far, and the genetic architecture of AD entails both additive and nonadditive contributions from these loci. To better understand nonadditive impact of single-nucleotide polymorphisms (SNPs) on AD risk, we examined individual, joint, and interacting (SNPxSNP) effects of 139 and 66 SNPs mapped to the BIN1 and MS4A6A AD-associated loci, respectively.
View Article and Find Full Text PDFGeroscience
January 2025
Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, 02111, USA.
Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk.
View Article and Find Full Text PDFBackground: Inclusions of TAR DNA binding protein of 43kDa (TDP-43) constitute the main characteristic pathology in the majority (∼97%) of amyotrophic lateral sclerosis (ALS) cases and approximately 50% of patients with frontotemporal lobar degeneration (FTLD). TDP-43 is a nuclear RNA binding protein; however, in disease, it becomes hyperphosphorylated and/or insoluble, hindering its nuclear function in maintaining RNA homeostasis. Importantly, the incidence of TDP-43 proteinopathy extends to aging brains (LATE) and may be concomitant with Alzheimer's disease (AD) neuropathological changes (LATE/AD) in up to 70% of AD patients.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia.
Background: Whilst numerous studies have explored the relationship between Alzheimer's disease (AD) and diabetes, there remains significant conflicting evidence as to their relationship. Some studies suggest an increased likelihood of developing AD in individuals with diabetes, especially type 2 diabetes (T2D) and that both diseases share pathological features. In contrast, other studies indicate that T2D is more aligned with vascular cognitive impairment and dementia and associated cerebrovascular/white matter pathology.
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