Surrogate Adiposity Markers and Mortality

JAMA Network Open, Год журнала: 2023, Номер 6(9), С. e2334836 - e2334836

Опубликована: Сен. 20, 2023

Body mass index (BMI) is an easily obtained adiposity surrogate. However, there variability in body composition and adipose tissue distribution between individuals with the same BMI, controversy regarding BMI associated lowest mortality risk.To evaluate which of fat (FMI), waist-to-hip (WHR) has strongest most consistent association mortality.This cohort study used incident deaths from UK Biobank (UKB; 2006-2022), includes data 22 clinical assessment centers across United Kingdom. UKB British participants White ancestry (N = 387 672) were partitioned into a discovery (n 337 078) validation 50 594), latter consisting 25 297 controls. The was to derive genetically determined measures while for analyses. Exposure-outcome associations analyzed through observational mendelian randomization (MR) analyses.BMI, FMI, WHR.All-cause cause-specific (cancer, cardiovascular disease [CVD], respiratory disease, or other causes) mortality.There 672 594 our (mean [SD] age, 56.9 [8.0] years; 177 340 [45.9%] male, 210 332 [54.2%], female), MR 61.6 [6.2] 30 031 [59.3%] 20 563 [40.6%], female) analyses, respectively. Associations measured FMI all-cause J-shaped, whereas WHR linear using hazard ratio (HR) scale (HR per SD increase WHR, 1.41 [95% CI, 1.38-1.43]). Genetically had stronger than (odds [OR] 1.51 1.32-1.72]; OR 1.29 1.20-1.38]; P heterogeneity .02). This male female (OR, 1.89 1.54-2.32]; .01). Unlike WHR-all-cause irrespective observed BMI.In this study, BMI. Clinical recommendations should consider focusing on compared mass.

Язык: Английский

---

Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Май 24, 2023

Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents leading cause mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade pathophysiological events following restoration blood flow reoxygenation, not only directly damages brain tissue, but also enhances series pathological signaling cascades, contributing to inflammation, further aggravate damage tissue. Paradoxically, there are still no effective methods prevent CI/RI, since detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, characterized by mitochondrial oxidative stress, Ca 2+ overload, iron dyshomeostasis, DNA (mtDNA) defects quality control (MQC) disruption, closely relevant process CI/RI. There increasing evidence that dysfunctions play vital roles in regulation programmed cell deaths (PCDs) such as ferroptosis PANoptosis, newly proposed conception unique form innate immune inflammatory death regulated multifaceted PANoptosome complexes. In present review, we highlight how this key event contributes response well modes during Neuroprotective agents targeting may serve promising treatment strategy alleviate serious secondary injuries. A comprehensive insight into dysfunctions-mediated PCDs can help provide strategies guide therapies CI/RI IS.

Язык: Английский

---

The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Янв. 28, 2024

Abstract Background This study used a bidirectional 2-sample Mendelian randomization to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery [CAD], stroke, ischemic heart failure). Methods Genetic associations with were obtained from genome-wide association (GWAS) summary statistics UK biobank (n = 395,718) cardio-metabolic largest available GWAS statistics. Inverse variance weighting (IVW) was conducted, weighted median, MR-Egger, MR-PRESSO as sensitivity analyses. We repeated this in opposite direction using instruments for disease. Results Genetically predicted not associated risk of obesity (P 0.148), hypertension 0.515), dyslipidemia 0.684), T2DM 0.631), CAD 0.199), stroke 0.314), 0.633), failure 0.708). Regarding reverse directions, we only found that genetically decreased levels IVW analysis (β= − 0.060, 95% CI 0.044 0.076; P 2.416e−14) there suggestive evidence 0.021, 0.003 0.039; 0.025). Sensitivity replication analyses showed stable findings. Conclusions Findings did support effect development disease, but can lead reduced number. These findings have implications biomarker clinical practice.

Язык: Английский

---

Mitochondrial DNA Copy Number as a Potential Biomarker for the Severity of Motor Symptoms and Prognosis in Parkinson's Disease

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Mitochondrial function influences Parkinson's disease (PD) through the accumulation of pathogenic alpha-synuclein, oxidative stress, impaired autophagy, and neuroinflammation. The mitochondrial DNA copy number (mtDNA-CN), representing copies within a cell, serves as an easily assessable proxy for function.

Язык: Английский

---

New insights from bidirectional Mendelian randomization: causal relationships between telomere length and mitochondrial DNA copy number in aging biomarkers

Aging, Год журнала: 2024, Номер unknown

Опубликована: Апрель 24, 2024

Mitochondrial DNA (mtDNA) copy number and telomere length (TL) are dynamic factors that have been linked to the aging process in organisms. However, causal relationship between these variables remains uncertain. In this research, instrumental (IVs) related mtDNA TL were obtained from publicly available genome-wide association studies (GWAS). Through bidirectional Mendelian randomization (MR) analysis, we examined potential factors. The forward with as exposure outcome, did not reveal a significant effect (

Язык: Английский

---

Mitochondrial DNA: Inherent Complexities Relevant to Genetic Analyses

Genes, Год журнала: 2024, Номер 15(5), С. 617 - 617

Опубликована: Май 12, 2024

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores complex role of mtDNA a variety studies, including genome-wide, epigenome-wide, and phenome-wide association with focus on its implications for human traits diseases. Here, we discuss structure gene-encoding properties mtDNA, along influence environmental factors epigenetic modifications function variability. Particularly significant are challenges posed by mtDNA's high mutation rate, heteroplasmy, copy number variations, their impact disease susceptibility population analyses. The also highlights recent advances methodological approaches that enhance our understanding associations, advocating refined research techniques accommodate complexities. By providing overview intricacies this paper underscores need an integrated approach to studies considers unique mitochondrial genetics. Our findings aim inform future encourage development innovative methodologies better interpret broad health disease.

Язык: Английский

---

Exploring the Causal Effects of Mineral Metabolism Disorders on Telomere and Mitochondrial DNA: A Bidirectional Two-Sample Mendelian Randomization Analysis

Nutrients, Год журнала: 2024, Номер 16(10), С. 1417 - 1417

Опубликована: Май 8, 2024

The aim of this study was to assess the causal relationships between mineral metabolism disorders, representative trace elements, and key aging biomarkers: telomere length (TL) mitochondrial DNA copy number (mtDNA-CN). Utilizing bidirectional Mendelian randomization (MR) analysis in combination with two-stage least squares (2SLS) method, we explored disorders these indicators. Sensitivity can be used determine reliability robustness research results. results confirmed that a positive relationship observed TL (p < 0.05), while mtDNA-CN not significant > 0.05). Focusing on subgroup analyses specific minerals, our findings indicated distinct iron both In contrast, magnesium phosphorus did exhibit effects either biomarker Moreover, reverse MR reveal any 2SLS further reinforced levels Notably, sensitivity indicate pleiotropy or heterogeneity within These highlight pivotal role cellular aging, particularly regulating sustaining mtDNA-CN, offering new insights into how influence biomarkers. Our underscores importance element balance, especially regarding intake, combating process. This provides potential strategy for slowing through adjustment laying groundwork future elements healthy aging.

Язык: Английский

---

UK Biobank—A Unique Resource for Discovery and Translation Research on Genetics and Neurologic Disease

Neurology Genetics, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 17, 2025

UK Biobank is a large-scale prospective study with extensive genetic and phenotypic data from half million adults. Participants, aged 40 to 69, were recruited the general population between 2006 2010. During recruitment, participants completed questionnaires covering lifestyle medical history, underwent physical measurements, provided biological samples for long-term storage. Whole-cohort assays have been conducted, including biochemical markers, genotyping, whole-exome whole-genome sequencing, as well proteomics metabolomics in large subsets of cohort, potential additional future. Participants consented link their electronic health records, enabling identification outcomes over time. Research studies using already enhanced our understanding role variation neurologic disease, offering insights into therapeutic approaches. The integration imaging has led significant discoveries regarding relationship variants brain structure function, particularly Alzheimer disease Parkinson disease. Genetic also allowed Mendelian randomization analyses be performed, further investigation causality associations behavioral physiologic factors-such diet blood pressure-and outcomes. Furthermore, proteomic useful identifying new drug targets enhancing risk prediction algorithms that are increasingly applied clinical practice identify those at higher risk. As continues enhanced, cases accrue time, will become valuable both discovery translational research on genetics

Язык: Английский

---

Mitochondrial DNA copy number and Alzheimer’s disease and Parkinson disease

Mitochondrion, Год журнала: 2025, Номер unknown, С. 102032 - 102032

Опубликована: Март 1, 2025

Язык: Английский

---

Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function

Neurology, Год журнала: 2023, Номер 100(18)

Опубликована: Март 16, 2023

Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association cognitive function MRI measures community-based samples middle-aged older adults.

Язык: Английский

---