A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities

American Journal of Respiratory and Critical Care Medicine, Год журнала: 2023, Номер 208(7), С. 791 - 801

Опубликована: Июль 31, 2023

Rationale: In addition to rare genetic variants and the MUC5B locus, common contribute idiopathic pulmonary fibrosis (IPF) risk. The predictive power of outside locus for IPF interstitial lung abnormalities (ILAs) is unknown. Objectives: We tested value polygenic risk scores (PRSs) with without region on IPF, ILA, ILA progression. Methods: developed PRSs that included (PRS-M5B) excluded (PRS-NO-M5B) (500-kb window around rs35705950-T) using an genome-wide association study. assessed PRS associations area under receiver operating characteristic curve (AUC) metrics Measurements Main Results: 14,650 participants (1,970 IPF; 1,068 ILA) from six multi-ancestry population-based case–control cohorts. cases study, PRS-M5B (odds ratio [OR] per SD score, 3.1; P = 7.1 × 10−95) PRS-NO-M5B (OR SD, 2.8; 2.5 10−87) were associated IPF. Participants in top quintile had ∼sevenfold odds compared those first quintile. A clinical model predicted (AUC, 0.61); rs35705950-T demonstrated higher AUCs (0.73 0.7, respectively), adding both predictors a yielded highest performance 0.81). was (OR, 1.25) progression 1.16) European ancestry participants. Conclusions: variant score complements identify individuals at high fibrosis.

Язык: Английский

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The One Health approach for allergic diseases and asthma

Allergy, Год журнала: 2023, Номер 78(7), С. 1777 - 1793

Опубликована: Апрель 29, 2023

Abstract The One Health approach is a collaborative and interdisciplinary strategy with focal point on human, animal, environmental health interconnections. can support the advanced management of allergic diseases asthma, as complex, multifactorial driven by interactions between resilience response to exposome. According concept asthma arising from exposures wide range allergens, infectious agents irritants (such pollutants) occurring indoors outdoors be heavily influenced (air, water, soil quality) intermingled animal health. These are currently impacted climate change, land use, urbanization, migration, overpopulation, many more. Thus, coordinated address underlying factors that contribute development needs focus environment, altogether. Collaborative efforts across multiple sectors, including public health, veterinary medicine, science, community engagement thus needed. A activities, monitoring surveillance data, targeted interventions reduce allergens irritants, research mechanisms drive needed move field forward. In this consensus document elaborated European Academy Allergy Clinical Immunology (EAACI) American Allergy, Asthma, (AAAAI) under practical allergy (PRACTALL) series, we provide insights into Heath aiming framework for addressing complex nature asthma.

Язык: Английский

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Genetics of chronic respiratory disease

Nature Reviews Genetics, Год журнала: 2024, Номер 25(8), С. 534 - 547

Опубликована: Март 6, 2024

Язык: Английский

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Precision Approaches to Chronic Obstructive Pulmonary Disease Management

Annual Review of Medicine, Год журнала: 2023, Номер 75(1), С. 247 - 262

Опубликована: Окт. 12, 2023

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD heterogeneity has hampered progress in developing pharmacotherapies that affect progression. This issue can be addressed by precision medicine approaches, which focus on understanding an individual's risk, tailoring management based pathobiology, environmental exposures, psychosocial issues. There urgent need to identify patients at high risk for poor outcomes understand mechanistic level why certain individuals are risk. Genetics, omics, network analytic techniques have started dissect with specific pathobiology. Drug repurposing approaches biomarkers inflammatory processes (i.e., type 2 inflammation) promising. As larger data sets, additional new analytical become available, there will enormous opportunities high-risk treat their pathophysiological derangements. These show great promise stratification, early intervention, drug repurposing, novel therapeutic COPD.

Язык: Английский

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A polygenic risk score and age of diagnosis of COPD

European Respiratory Journal, Год журнала: 2022, Номер 60(3), С. 2101954 - 2101954

Опубликована: Фев. 3, 2022

Background Genetic susceptibility may be associated with earlier onset of chronic obstructive pulmonary disease (COPD). We hypothesised that a polygenic risk score (PRS) for COPD would age diagnosis COPD. Methods In 6647 non-Hispanic White (NHW) and 2464 African American (AA) participants from COPDGene, 6812 the Framingham Heart Study (FHS), we tested relationship PRS diagnosis. Age at was determined by: 1) self-reported or 2) visits when moderate-to-severe airflow limitation (Global Initiative Chronic Obstructive Lung Disease (GOLD) grade 2–4) observed on spirometry. used Cox regression to examine overall time-dependent effects incident COPDGene study, also examined PRS's predictive value <50 years (COPD50) using logistic area under curve (AUC) analyses, without addition other factors present early life ( e.g. childhood asthma). Results models, demonstrated age-dependent associations COPD, larger younger ages in both cohorts. The COPD50 (OR 1.55 (95% CI 1.41–1.71) NHW, OR 1.23 1.05–1.43) AA 2.47 2.12–2.88) FHS participants). adding known early-life improved prediction NHW (AUC 0.69 versus 0.74; p<0.0001) 0.61 0.64; p=0.04) participants. Conclusions A is retains added factors.

Язык: Английский

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Age-related loss of chromosome Y is associated with levels of sex hormone binding globulin and clonal hematopoiesis defined by TET2 , TP53 , and CBL mutations

Science Advances, Год журнала: 2023, Номер 9(16)

Опубликована: Апрель 21, 2023

Mosaic loss of the Y-chromosome (LOY) in peripheral blood leukocytes is most common somatic alteration men and linked to wide range malignant nonmalignant conditions. LOY associated with age, smoking, constitutional genetics. Here, we aimed assess relationships between LOY, serum biomarkers, clonal hematopoiesis (CH). U.K. Biobank was strongly levels sex hormone binding globulin (SHBG), a key regulator testosterone bioavailability. Mendelian randomization suggested causal effect SHBG on but there no evidence for an SHBG. In contrast, age-related CH defined by driver mutations not at fractions above 30%. TET2, TP53, CBL were enriched cases, JAK2 V617F depleted. Our findings thus identify independent levels, CH.

Язык: Английский

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Exploring the genetics of airflow limitation in lung function across the lifespan – a polygenic risk score study

EClinicalMedicine, Год журнала: 2024, Номер 75, С. 102731 - 102731

Опубликована: Авг. 12, 2024

Язык: Английский

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PM2.5 increases the risk of early-onset COPD mediated by smoking and shared genes: a large-scale genetic analysis

Clinical and Experimental Medicine, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 12, 2025

Язык: Английский

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Regional lung function assessment using electrical impedance tomography in COPD, PRISm, and normal spirometry subjects: insights into early diagnostic potential

BMC Pulmonary Medicine, Год журнала: 2025, Номер 25(1)

Опубликована: Май 5, 2025

Abstract Purpose This study utilizes electrical impedance tomography (EIT) to explore spatial–temporal heterogeneity in regional lung function among patients with chronic obstructive disease (COPD), preserved ratio impaired spirometry (PRISm), and those normal function. Methods Subjects who had pulmonary test at Sir Run Shaw Hospital from 28 December 2023 30 March 2024 were screened. Regional functions accessed EIT regarding spatial distribution, abnormal area size, expiratory time. The correlations between smoking index, SGRQ score, EIT-related parameters also evaluated. Results A total of 194 screened 161 included (56 COPD, 21 PRISm, 84 normal). Spatial distribution FEV1EIT ( P < 0.001), FVCEIT = 0.025), FEV1/FVCEIT MMEFEIT 0.012), T-75EIT FIVCEIT 0.020) showed significant differences the three groups. percentage areas detected via was 83.40% (25–75% percentiles 52.29%-98.39%) COPD group, 25.46% (17.31%-41.31%) PRISm 10.37% (3.34%-19.04%) group. time constant map revealed that exhibited longest exhalation times. Elevated index scores associated increased larger FEV1/FVCEIT. Conclusion Through EIT-based assessment, it is possible sensitively identify spatio-temporal patients. impairments, particularly an FEV1/FVC ≥ 0.7, using EIT, highlighting its potential for early diagnosis.

Язык: Английский

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PIGEON: a statistical framework for estimating gene–environment interaction for polygenic traits

Nature Human Behaviour, Год журнала: 2025, Номер unknown

Опубликована: Май 23, 2025

Язык: Английский

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