المؤلفون: Wilcox, N., Wahlström, C., Kvist, A., Simard, J.

المصدر: Nature Genetics. 55(9):1435-1439

مصطلحات موضوعية: Exome, Exome Sequencing, Female, Humans, Mutation, Missense, Neoplasms, ATM protein, ATR protein, BRCA1 associated ring domain protein 1, BRCA1 protein, BRCA2 protein, checkpoint kinase 2, partner and localizer of BRCA2, adult, Article, breast cancer, cancer risk, cancer susceptibility, controlled study, female, gene frequency, gene identification, genetic association, genetic linkage, genetic susceptibility, genetic variability, human, lztr1 gene, major clinical study, map3k1 gene, missense mutation, oncogene, whole exome sequencing, exome, genetics, meta analysis, neoplasm, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik, Medical and Health Sciences, Basic Medicine, Medical Genetics, Klinisk medicin, Cancer och onkologi, Clinical Medicine, Cancer and Oncology

الوصف: Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P < 2.5 × 10−6): the five known susceptibility genes ATM, BRCA1, BRCA2, CHEK2 and PALB2, together with MAP3K1. Associations were also observed for LZTR1, ATR and BARD1 with P < 1 × 10−4. Associations between predicted deleterious rare missense or protein-truncating variants and breast cancer were additionally identified for CDKN2A at exome-wide significance. The overall contribution of coding variants in genes beyond the previously known genes is estimated to be small. © 2023, The Author(s).

الوصول الحر: https://lup.lub.lu.se/record/69c36c9b-10ee-4f40-8800-b6aec24ba791Test
http://dx.doi.org/10.1038/s41588-023-01466-zTest

المؤلفون: León-Reyes, Guadalupe, Argoty-Pantoja, Anna D, Rivera-Paredez, Berenice, Hidalgo-Bravo, Alberto, Flores, Yvonne N, Salmerón, Jorge, Velázquez-Cruz, Rafael

المصدر: Nutrients. 15(2)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Public Health, Health Sciences, Clinical Sciences, Nutrition and Dietetics, Cardiovascular, Genetics, Nutrition, Prevention, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Humans, Adult, Female, Cohort Studies, Cholesterol, HDL, Diet, Alleles, Nutrients, ATP Binding Cassette Transporter 1, Nucleotide Transport Proteins, hypoalphalipoproteinemia, gene-gene interaction, gene-diet interaction, rs17120425, rs1784042, rs9282541, Mexican population, gene–diet interaction, gene–gene interaction, Food Sciences, Clinical sciences, Nutrition and dietetics, Public health

الوصف: Previous studies have reported that the SIDT2 and ABCA1 genes are involved in lipid metabolism. We aimed to analyze the association-the gene x gene interaction between rs17120425 and rs1784042 on SIDT2 and rs9282541 on ABCA1 and their diet interaction on the HDL-c serum levels-in a cohort of 1982 Mexican adults from the Health Workers Cohort Study. Demographic and clinical data were collected through a structured questionnaire and standardized procedures. Genotyping was performed using a predesigned TaqMan assay. The associations and interactions of interest were estimated using linear and logistic regression. Carriers of the rs17120425-A and rs1784042-A alleles had slightly higher blood HDL-c levels compared to the non-carriers. In contrast, rs9282541-A was associated with low blood HDL-c levels (OR = 1.34, p = 0.013). The rs1784042 x rs9282541 interaction was associated with high blood HDL-c levels (p = 3.4 × 10-4). Premenopausal women who carried at least one rs17120425-A allele and consumed high dietary fat, protein, monounsaturated, or polyunsaturated fatty acids levels had higher HDL-c levels than the non-carriers. These results support the association between the genetic variants on SIDT2 and ABCA1 with HDL-c levels and suggest gene-gene and gene-diet interactions over HDL-c concentrations in Mexican adults. Our findings could be a platform for developing clinical and dietary strategies for improving the health of the Mexican population.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0b78s714Test

المؤلفون: Columbres, Rod Carlo Agram, Chin, Yue, Pratti, Sanjana, Quinn, Colin, Gonzalez-Cuyar, Luis F, Weiss, Michael, Quintero-Rivera, Fabiola, Kimonis, Virginia

المصدر: Genes. 14(3)

مصطلحات موضوعية: Biological Sciences, Genetics, Rare Diseases, Neurodegenerative, Aging, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Humans, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Osteitis Deformans, Valosin Containing Protein, Cell Cycle Proteins, Merozoite Surface Protein 1, Myositis, Inclusion Body, valosin-containing protein, VCP, IBMPFD, ALS, multisystem proteinopathy-1, MSP1

الوصف: Valosin-containing protein (VCP) gene mutations have been associated with a rare autosomal dominant, adult-onset progressive disease known as multisystem proteinopathy 1 (MSP1), or inclusion body myopathy (IBM), Paget's disease of bone (PDB), frontotemporal dementia (FTD), (IBMPFD), and amyotrophic lateral sclerosis (ALS). We report the clinical and genetic analysis findings in five patients, three from the same family, with novel VCP gene variants: NM_007126.5 c.1106T>C (p.I369T), c.478G>A (p.A160T), and c.760A>T (p.I254F), associated with cardinal MSP1 manifestations including myopathy, PDB, and FTD. Our report adds to the spectrum of heterozygous pathogenic variants found in the VCP gene and the high degree of clinical heterogeneity. This case series prompts increased awareness and early consideration of MSP1 in the differential diagnosis of myopathies and/or PDB, dementia, or ALS to improve the diagnosis and early management of clinical symptoms.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4dj0h013Test

المؤلفون: Perry, Lauren M, Cruz, Sylvia M, Kleber, Kara T, Judge, Sean J, Darrow, Morgan A, Jones, Louis B, Basmaci, Ugur N, Joshi, Nikhil, Settles, Matthew L, Durbin-Johnson, Blythe P, Gingrich, Alicia A, Monjazeb, Arta Monir, Carr-Ascher, Janai, Thorpe, Steve W, Murphy, William J, Eisen, Jonathan A, Canter, Robert J

المصدر: Journal for ImmunoTherapy of Cancer. 11(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Human Genome, Vaccine Related, Clinical Research, Genetics, Cancer, Adult, Humans, Virome, Sarcoma, Prognosis, Extremities, Killer Cells, Natural, Soft Tissue Neoplasms, Tumor Microenvironment, sarcoma, immunomodulation, immunotherapy, programmed cell death 1 receptor, tumor biomarkers, Oncology and carcinogenesis

الوصف: BackgroundGroundbreaking studies have linked the gut microbiome with immune homeostasis and antitumor immune responses. Mounting evidence has also demonstrated an intratumoral microbiome, including in soft tissue sarcomas (STS), although detailed characterization of the STS intratumoral microbiome is limited. We sought to characterize the intratumoral microbiome in patients with STS undergoing preoperative radiotherapy and surgery, hypothesizing the presence of a distinct intratumoral microbiome with potentially clinically significant microbial signatures.MethodsWe prospectively obtained tumor and stool samples from adult patients with non-metastatic STS using a strict sterile collection protocol to minimize contamination. Metagenomic classification was used to estimate abundance using genus and species taxonomic levels across all classified organisms, and data were analyzed with respect to clinicopathologic factors.ResultsFifteen patients were enrolled. Most tumors were located at an extremity (67%) and were histologic grade 3 (87%). 40% were well-differentiated/dedifferentiated liposarcoma histology. With a median follow-up of 24 months, 4 (27%) patients developed metastases, and 3 (20%) died. Despite overwhelming human DNA (>99%) intratumorally, we detected a small but consistent proportion of bacterial DNA (0.02-0.03%) in all tumors, including Proteobacteria, Bacteroidetes, and Firmicutes, as well as viral species. In the tumor microenvironment, we observed a strong positive correlation between viral relative abundance and natural killer (NK) infiltration, and higher NK infiltration was associated with superior metastasis-free and overall survival by immunohistochemical, flow cytometry, and multiplex immunofluorescence analyses.ConclusionsWe prospectively demonstrate the presence of a distinct and measurable intratumoral microbiome in patients with STS at multiple time points. Our data suggest that the STS tumor microbiome has prognostic significance with viral relative abundance associated with NK infiltration and oncologic outcome. Additional studies are warranted to further assess the clinical impact of these findings.

الوصول الحر: https://escholarship.org/uc/item/0m8443xqTest

المؤلفون: Ogura, Koichi, Elkrief, Arielle, Bowman, Anita S, Koche, Richard P, de Stanchina, Elisa, Benayed, Ryma, Mauguen, Audrey, Mattar, Marissa S, Khodos, Inna, Meyers, Paul A, Healey, John H, Tap, William D, Hameed, Meera, Zehir, Ahmet, Shukla, Neerav, Sawyers, Charles, Bose, Rohit, Slotkin, Emily, Ladanyi, Marc

المصدر: JCO Precision Oncology. 6(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Pediatric Cancer, Genetics, Human Genome, Pediatric, Clinical Research, Cancer, 2.1 Biological and endogenous factors, Aetiology, Adult, Biological Products, Genomics, Humans, Mutation, Neuroectodermal Tumors, Primitive, Peripheral, Prospective Studies, Receptor, Fibroblast Growth Factor, Type 1, Repressor Proteins, Sarcoma, Ewing, United States, Oncology and carcinogenesis

الوصف: PurposeEwing sarcoma (ES) is a primitive sarcoma defined by EWSR1-ETS fusions as the primary driver alteration. To better define the landscape of cooperating secondary genetic alterations in ES, we analyzed clinical genomic profiling data of 113 patients with ES, a cohort including more adult patients (> 18 years) and more patients with advanced stage at presentation than previous genomic cohorts.MethodsThe data set consisted of patients with ES prospectively tested with the US Food and Drug Administration-cleared Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets large panel, hybrid capture-based next-generation sequencing assay. To assess the functional significance of ERF loss, we generated ES cell lines with increased expression of ERF and lines with knockdown of ERF. We assessed cell viability, clonogenic growth, and motility in these ES lines and performed transcriptomic and epigenetic analyses. Finally, we validated our findings in vivo using cell line xenografts.ResultsNovel subsets were defined by recurrent secondary alterations in ERF, which encodes an ETS domain transcriptional repressor, in 7% of patients (five truncating mutations, one deep deletion, and two missense mutations) and in FGFR1 in another 2.7% (one amplification and two known activating mutations). ERF alterations were nonoverlapping with STAG2 alterations. In vitro, increased expression of ERF decreased tumor cell growth, colony formation, and motility in two ES cell lines, whereas ERF loss induced cellular proliferation and clonogenic growth. Transcriptomic analysis of cell lines with ERF loss revealed an increased expression of genes and pathways associated with aggressive tumor biology, and epigenetic, chromatin-based studies revealed that ERF competes with EWSR1-FLI1 at ETS-binding sites.ConclusionOur findings open avenues to new insights into ES pathobiology and to novel therapeutic approaches in a subset of patients with ES.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/76p9d7skTest

المؤلفون: Murray, Matthew

مصطلحات موضوعية: 32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis, Rare Diseases, Digestive Diseases, Genetics, Cancer, Clinical Research, Pediatric, 2.4 Surveillance and distribution, 2 Aetiology, 2.1 Biological and endogenous factors, Humans, Male, Female, Child, Preschool, Neoplastic Syndromes, Hereditary, Cross-Sectional Studies, Adolescent, Brain Neoplasms, DNA Mismatch Repair, Longitudinal Studies, Colorectal Neoplasms, Incidence, MutS Homolog 2 Protein, MutL Protein Homolog 1, Adult, Young Adult, Mutation

الوصف: Background: Constitutional mismatch-repair deficiency (CMMRD) is an aggressive cancer-predisposition syndrome caused by biallelic pathogenic variants in PMS2, MSH6, MLH1, and MSH2. Lack of robust data on the true clinical-spectrum, cancerbiology, and genotype-phenotype associations result in challenges in management and inferior patient outcomes. Methods: The International Replication-Repair Deficiency Consortium performed comprehensive clinical and molecular analyses for CMMRD patients longitudinally between 2008-2022 and investigated the impact of genotype and cancer-biology on patient survival. Findings: Data on 201 patients from 27 countries demonstrated high homozygosity in countries with low consanguinity, particularly among minorities. Dermatological manifestations were frequent (93%), with 28% fulfilling clinical criteria for neurofibromatosis-type-1. One-hundred-and-ninety-four (97%) patients developed 339 cancers, with cumulative cancer incidence reaching 90% by age-18 and 100% by age- 40. The 2nd-cancer incidence was 49% within 10-years after first cancer diagnosis. Median time to a new cancer was 2-years. An expanded neoplastic spectrum included previously unreported, and early-onset, adult-type, breast, prostate, and pancreatic cancers by the 3rd-decade. The cancers exhibited universal hypermutation, high microsatellite instability, and corresponding mutational signatures. A significant difference in mutational burden between cancer types was related to somatic mutations in POLE/POLD1 and TP53, which were enriched in brain tumors, contributing to poor 10-year survival (39%; p<0.0001). MLH1/MSH2 genotypes had an earlier cancer-onset than PMS2/MSH6, and inferior patient survival (15-years overall survival: PMS2: 63%, MSH6: 49%, MLH1: 19%,MSH2: 0%; p<0.0001). Truncating mutations resulted in earlier cancers and poor outcomes even within the same gene (p<0.0001). Although surveillance and immunotherapy improved outcomes, the deleterious impact of specific genotypes persisted. Interpretation: ...

وصف الملف: application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/363659Test; https://doi.org/10.17863/CAM.105580Test

الإتاحة: https://doi.org/10.17863/CAM.105580Test
https://www.repository.cam.ac.uk/handle/1810/363659Test

المؤلفون: Kim, Jaehwan, Moreno, Ariana, Krueger, James G

مصطلحات موضوعية: Biomedical and Clinical Sciences, Immunology, Clinical Research, Clinical Trials and Supportive Activities, Autoimmune Disease, Psoriasis, Biotechnology, Skin, Inflammatory and immune system, Adult, Biological Products, Cytokines, Humans, Interleukin-17, Th17 Cells, psoriasis, type 17 T-cells, regulator T-cell, type 1 regulatory T-cell, regulatory dendritic cell, immune tolerance, immune homeostasis, Medical Microbiology, Biochemistry and cell biology, Genetics

الوصف: Psoriasis vulgaris is a common inflammatory disease affecting 7.5 million adults just in the US. Previously, psoriasis immunopathogenesis has been viewed as the imbalance between CD4+ T-helper 17 (Th17) cells and regulatory T-cells (Tregs). However, current paradigms are rapidly evolving as new technologies to study immune cell subsets in the skin have been advanced. For example, recently minted single-cell RNA sequencing technology has provided the opportunity to compare highly differing transcriptomes of Type 17 T-cell (T17 cell) subsets depending on IL-17A vs. IL-17F expression. The expression of regulatory cytokines in T17 cell subsets provided evidence of T-cell plasticity between T17 cells and regulatory T-cells (Tregs) in humans. In addition to Tregs, other types of regulatory cells in the skin have been elucidated, including type 1 regulatory T-cells (Tr1 cells) and regulatory dendritic cells. More recently, investigators are attempting to apply single-cell technologies to clinical trials of biologics to test if monoclonal blockade of pathogenic T-cells will induce expansion of regulatory immune cell subsets involved in skin homeostasis.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/35n6v8d5Test

المؤلفون: Smyth, LJ, Kilner, J, Nair, V, Liu, H, Brennan, E, Kerr, K, Sandholm, N, Cole, J, Dahlström, E, Syreeni, A, Salem, RM, Nelson, RG, Looker, HC, Wooster, C, Anderson, K, McKay, GJ, Kee, F, Young, I, Andrews, D, Forsblom, C, Hirschhorn, JN, Godson, C, Groop, PH, Maxwell, AP, Susztak, K, Kretzler, M, Florez, JC, McKnight, AJ

المصدر: Clinical Epigenetics. 13(1)

مصطلحات موضوعية: Biological Sciences, Genetics, Autoimmune Disease, Diabetes, Biotechnology, Kidney Disease, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Renal and urogenital, Good Health and Well Being, Adult, DNA Methylation, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Epigenesis, Genetic, Epigenomics, Female, Humans, Kidney Failure, Chronic, Male, Association, EPIC, End-stage, Kidney, Methylation, Nephropathy, Clinical Sciences, Paediatrics and Reproductive Medicine

الوصف: BackgroundA subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina's Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10-8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM.ResultsTop-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation.ConclusionsEpigenetic alterations provide a dynamic link between an individual's genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5rm9447bTest

المؤلفون: Rutsch, Niklas, Chamberlain, Chester E, Dixon, Wesley, Spector, Lauren, Letourneau-Freiberg, Lisa R, Lwin, Wint W, Philipson, Louis H, Zarbock, Alexander, Saintus, Karline, Wang, Juehu, German, Michael S, Anderson, Mark S, Lowell, Clifford A

المصدر: Diabetes Care. 44(8)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Immunology, Genetics, Prevention, Human Genome, Pediatric, Autoimmune Disease, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Inflammatory and immune system, Adult, Autoimmune Diseases, Diabetes Mellitus, Type 1, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Mutation, Phenotype, Young Adult, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences

الوصف: ObjectiveMultiple genome-wide association studies have identified a strong genetic linkage between the SKAP2 locus and type 1 diabetes (T1D), but how this leads to disease remains obscure. Here, we characterized the functional consequence of a novel SKAP2 coding mutation in a patient with T1D to gain further insight into how this impacts immune tolerance.Research design and methodsWe identified a 24-year-old individual with T1D and other autoimmune and inflammatory conditions. The proband and first-degree relatives were recruited for whole-exome sequencing. Functional studies of the protein variant were performed using a cell line and primary myeloid immune cells collected from family members.ResultsSequencing identified a de novo SKAP2 variant (c.457G>A, p.Gly153Arg) in the proband. Assays using monocyte-derived macrophages from the individual revealed enhanced activity of integrin pathways and a migratory phenotype in the absence of chemokine stimulation, consistent with SKAP2 p.Gly153Arg being constitutively active. The p.Gly153Arg variant, located in the well-conserved lipid-binding loop, induced similar phenotypes when expressed in a human macrophage cell line. SKAP2 p.Gly153Arg is a gain-of-function, pathogenic mutation that disrupts myeloid immune cell function, likely resulting in a break in immune tolerance and T1D.ConclusionsSKAP2 plays a key role in myeloid cell activation and migration. This particular mutation in a patient with T1D and multiple autoimmune conditions implicates a role for activating SKAP2 variants in autoimmune T1D.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3wj7t144Test

المؤلفون: Roshandel, Delnaz, Chen, Zhuo, Canty, Angelo J, Bull, Shelley B, Natarajan, Rama, Paterson, Andrew D

المصدر: Clinical Epigenetics. 12(1)

مصطلحات موضوعية: Prevention, Autoimmune Disease, Diabetes, Neurosciences, Peripheral Neuropathy, Cardiovascular, Heart Disease, Metabolic and endocrine, Good Health and Well Being, Adolescent, Adult, Albumins, CpG Islands, DNA Methylation, Diabetes Mellitus, Type 1, Diabetic Neuropathies, Epigenesis, Genetic, Female, Genome-Wide Association Study, Humans, Male, Oligonucleotide Array Sequence Analysis, Young Adult, DNA methylation age, Type 1 diabetes, Diabetic complications, DCCT/EDIC Research Group, Genetics, Clinical Sciences, Paediatrics and Reproductive Medicine

الوصف: BackgroundMany CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated.ResultsPan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E-3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = - 1.99, p = 0.045) and leisure time (β = - 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E-50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used.ConclusionsVarious methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5k95n6skTest