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Article ; Online: Bi-directional association of rheumatoid arthritis and chronic obstructive pulmonary disease: Linking arthritis, inflammation, smoking, airways disease, and emphysema.

Ford, Julia A / Cho, Michael H / Sparks, Jeffrey A

2024

Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keae137
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Article ; Online: Who Modifies the Modifiers: A High-Resolution View of the Genetic Modifiers of Cystic Fibrosis.

Kalra, Sean / Cho, Michael H

American journal of respiratory and critical care medicine

2023 Volume 207, Issue 10, Page(s) 1261–1262

MeSH term(s)	Humans ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Patient Acuity ; Lung
Chemical Substances	Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202303-0468ED
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Article ; Online: Disturbance of sleep maintenance, but not sleep duration, activates nuclear factor-κB and signal transducer and activator of transcription family proteins in older adults: sex differences.

Piber, Dominique / Olmstead, Richard / Cho, Joshua H / Irwin, Michael R

Sleep

2023 Volume 46, Issue 10

Abstract: Study objectives: Disturbances of sleep maintenance and sleep duration are common in older adults and associated with an increased risk for age-related mortality and morbidity. Converging evidence implicates inflammation as an underlying mechanism, ... ...

Abstract	Study objectives: Disturbances of sleep maintenance and sleep duration are common in older adults and associated with an increased risk for age-related mortality and morbidity. Converging evidence implicates inflammation as an underlying mechanism, especially in females. However, it is unknown what specific aspects of sleep disturbance impact inflammatory mechanisms in older adults. Methods: Using data from community-dwelling older adults who participated in the Sleep Health and Aging Research (SHARE) field study (n = 262, mean age 71.9 ± 8.0 years), we conducted a secondary analysis to examine whether disturbance of sleep maintenance (i.e. greater amount of wake time after sleep onset [WASO]) and sleep duration (i.e. shorter total sleep time [TST]) assessed by sleep diary and actigraphy are associated with greater activation of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT) family proteins STAT1, STAT3, and STAT5 in peripheral blood monocytic cells. In addition, moderation effects of sex were explored. Results: Data were available for sleep diary (n = 82), actigraphy (n = 74), and inflammatory signaling and transcriptional measures (n = 132). As assessed by sleep diary, greater amount of WASO (β = 0.39, p < 0.01), but not TST, was associated with higher levels of NF-κB. Whereas diary-assessed sleep measures were not associated with STAT family proteins, a moderation analysis revealed that greater diary-assessed WASO was associated with higher levels of STAT1 (p < 0.05), STAT3 (p < 0.05), and STAT5 (p < 0.01) in females, but not in males. Actigraphy-assessed sleep measures were not associated either with NF-κB or STAT activation. Conclusions: In older adults, self-reported disturbance of sleep maintenance assessed by sleep diary was uniquely associated with higher levels of NF-κB, along with higher levels of STAT family proteins in females, but not in males. Our data suggest that improvingself-reported sleep maintenance might mitigate age-related increases in inflammatory signaling and transcriptional pathways, possibly more strongly in females, with the potential to reduce mortality risk in older adults.
MeSH term(s)	Humans ; Male ; Female ; Aged ; Middle Aged ; NF-kappa B ; STAT5 Transcription Factor ; Sex Characteristics ; Sleep/physiology ; Polysomnography ; Actigraphy ; Sleep Initiation and Maintenance Disorders
Chemical Substances	NF-kappa B ; STAT5 Transcription Factor
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	424441-2
ISSN	1550-9109 ; 0161-8105
ISSN (online)	1550-9109
ISSN	0161-8105
DOI	10.1093/sleep/zsad130
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Article ; Online: Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder.

Cho, Michael H / Hobbs, Brian D / Silverman, Edwin K

The Lancet. Respiratory medicine

2022 Volume 10, Issue 5, Page(s) 485–496

Abstract: Chronic obstructive pulmonary disease (COPD) is a deadly and highly morbid disease. Susceptibility to and heterogeneity of COPD are incompletely explained by environmental factors such as cigarette smoking. Family-based and population-based studies have ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is a deadly and highly morbid disease. Susceptibility to and heterogeneity of COPD are incompletely explained by environmental factors such as cigarette smoking. Family-based and population-based studies have shown that a substantial proportion of COPD risk is related to genetic variation. Genetic association studies have identified hundreds of genetic variants that affect risk for COPD, decreased lung function, and other COPD-related traits. These genetic variants are associated with other pulmonary and non-pulmonary traits, demonstrate a genetic basis for at least part of COPD heterogeneity, have a substantial effect on COPD risk in aggregate, implicate early-life events in COPD pathogenesis, and often involve genes not previously suspected to have a role in COPD. Additional progress will require larger genetic studies with more ancestral diversity, improved profiling of rare variants, and better statistical methods. Through integration of genetic data with other omics data and comprehensive COPD phenotypes, as well as functional description of causal mechanisms for genetic risk variants, COPD genetics will continue to inform novel approaches to understanding the pathobiology of COPD and developing new strategies for management and treatment.
MeSH term(s)	Cigarette Smoking ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Lung ; Phenotype ; Pulmonary Disease, Chronic Obstructive/genetics
Language	English
Publishing date	2022-04-12
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2686754-0
ISSN	2213-2619 ; 2213-2600
ISSN (online)	2213-2619
ISSN	2213-2600
DOI	10.1016/S2213-2600(21)00510-5
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Article ; Online: Reply.

Prisco, Lauren / Moll, Matthew / Doyle, Tracey J / Cho, Michael H / Sparks, Jeffrey A

Arthritis & rheumatology (Hoboken, N.J.)

2022 Volume 74, Issue 6, Page(s) 1096–1097

Language	English
Publishing date	2022-04-28
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.42086
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Article: Why is Disease Penetration So Variable? Role of Genetic Modifiers of Lung Function in Alpha-1 Antitrypsin Deficiency.

Hobbs, Brian D / Cho, Michael H

Chronic obstructive pulmonary diseases (Miami, Fla.)

2020 Volume 7, Issue 3, Page(s) 214–223

Abstract: Individuals with alpha-1 antitrypsin deficiency (AATD) have marked heterogeneity in lung function, suspected to be related to a combination of both environmental (e.g., cigarette smoking) and genetic factors. Lung function is heritable in the general ... ...

Abstract	Individuals with alpha-1 antitrypsin deficiency (AATD) have marked heterogeneity in lung function, suspected to be related to a combination of both environmental (e.g., cigarette smoking) and genetic factors. Lung function is heritable in the general population and in persons with severe AATD. Several genetic modifiers of lung function in persons with AATD have been described; however, replication is lacking. A genome-wide association study (GWAS) of lung function in persons with AATD has yet to be performed and may inform whether genetic determinants of lung function are overlapping in persons with AATD and in the general population. As GWASs require large sample sizes for adequate power, genetic risk scores offer an alternate approach to assess the overlap of genetic determinants of lung function in the general population in persons with AATD. Where GWASs are limited to common genetic variant discovery, whole genome sequencing (for rare variant discovery) and integrative genomic studies (examining the influence of genetic variants on gene, protein, and metabolite levels) offer potential for an expanded discovery of genetic modifiers of lung function in AATD. In the following review we examine past descriptions of genetic modifiers of lung function in AATD and describe a path forward to further investigate and define the likely genetic modifiers of lung function in AATD.
Language	English
Publishing date	2020-09-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2771715-X
ISSN	2372-952X
ISSN	2372-952X
DOI	10.15326/jcopdf.7.3.2019.0159
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Article: Clinical relevance of lung function trajectory clusters in middle-aged and older adults.

Bertels, Xander / Ross, James C / Faner, Rosa / Cho, Michael H / Ikram, M Arfan / Brusselle, Guy G / Lahousse, Lies

ERJ open research

2024 Volume 10, Issue 1

Abstract: Background: The determinants and health outcomes of lung function trajectories in adults among the general population are poorly understood. We aimed to identify and characterise clusters of lung function trajectories in adults aged ≥45 years.: ... ...

Abstract	Background: The determinants and health outcomes of lung function trajectories in adults among the general population are poorly understood. We aimed to identify and characterise clusters of lung function trajectories in adults aged ≥45 years. Methods: Gaussian finite-mixture modelling was applied to baseline and annualised change of forced expiratory volume in 1 s (FEV Results: We identified eight trajectory clusters, with the reference group having persistently normal spirometry (prevalence 42.8%). Three clusters showed higher mortality, adjusted for confounders: 1) the persistently low FEV Conclusions: This study reveals clinically relevant lung function trajectory clusters in older adults of the general population.
Language	English
Publishing date	2024-02-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00793-2023
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Article ; Online: Towards an integrative genomics of lung function.

Cho, Michael H

The Lancet. Respiratory medicine

2015 Volume 3, Issue 10, Page(s) 739–741

MeSH term(s)	Female ; Genome-Wide Association Study/methods ; Humans ; Lung/physiopathology ; Male ; Pulmonary Disease, Chronic Obstructive/genetics
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Comment ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2686754-0
ISSN	2213-2619 ; 2213-2600
ISSN (online)	2213-2619
ISSN	2213-2600
DOI	10.1016/S2213-2600(15)00362-8
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Article ; Online: Fast computation of the eigensystem of genomic similarity matrices.

Hahn, Georg / Lutz, Sharon M / Hecker, Julian / Prokopenko, Dmitry / Cho, Michael H / Silverman, Edwin K / Weiss, Scott T / Lange, Christoph

BMC bioinformatics

2024 Volume 25, Issue 1, Page(s) 43

Abstract: The computation of a similarity measure for genomic data is a standard tool in computational genetics. The principal components of such matrices are routinely used to correct for biases due to confounding by population stratification, for instance in ... ...

Abstract	The computation of a similarity measure for genomic data is a standard tool in computational genetics. The principal components of such matrices are routinely used to correct for biases due to confounding by population stratification, for instance in linear regressions. However, the calculation of both a similarity matrix and its singular value decomposition (SVD) are computationally intensive. The contribution of this article is threefold. First, we demonstrate that the calculation of three matrices (called the covariance matrix, the weighted Jaccard matrix, and the genomic relationship matrix) can be reformulated in a unified way which allows for the application of a randomized SVD algorithm, which is faster than the traditional computation. The fast SVD algorithm we present is adapted from an existing randomized SVD algorithm and ensures that all computations are carried out in sparse matrix algebra. The algorithm only assumes that row-wise and column-wise subtraction and multiplication of a vector with a sparse matrix is available, an operation that is efficiently implemented in common sparse matrix packages. An exception is the so-called Jaccard matrix, which does not have a structure applicable for the fast SVD algorithm. Second, an approximate Jaccard matrix is introduced to which the fast SVD computation is applicable. Third, we establish guaranteed theoretical bounds on the accuracy (in [Formula: see text] norm and angle) between the principal components of the Jaccard matrix and the ones of our proposed approximation, thus putting the proposed Jaccard approximation on a solid mathematical foundation, and derive the theoretical runtime of our algorithm. We illustrate that the approximation error is low in practice and empirically verify the theoretical runtime scalings on both simulated data and data of the 1000 Genome Project.
MeSH term(s)	Genome ; Genomics ; Algorithms ; Linear Models
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-024-05650-8
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Article ; Online: Colocalization analysis of 3' UTR alternative polyadenylation quantitative trait loci reveals novel mechanisms underlying associations with lung function.

Saferali, Aabida / Kim, Wonji / Xu, Zhonghui / Chase, Robert P / Cho, Michael H / Laederach, Alain / Castaldi, Peter J / Hersh, Craig P

Human molecular genetics

2024

Abstract: While many disease-associated single nucleotide polymorphisms (SNPs) are expression quantitative trait loci (eQTLs), a large proportion of genome-wide association study (GWAS) variants are of unknown function. Alternative polyadenylation (APA) plays an ... ...

Abstract	While many disease-associated single nucleotide polymorphisms (SNPs) are expression quantitative trait loci (eQTLs), a large proportion of genome-wide association study (GWAS) variants are of unknown function. Alternative polyadenylation (APA) plays an important role in posttranscriptional regulation by allowing genes to shorten or extend 3' untranslated regions (UTRs). We hypothesized that genetic variants that affect APA in lung tissue may lend insight into the function of respiratory associated GWAS loci. We generated alternative polyadenylation (apa) QTLs using RNA sequencing and whole genome sequencing on 1241 subjects from the Lung Tissue Research Consortium (LTRC) as part of the NHLBI TOPMed project. We identified 56 179 APA sites corresponding to 13 582 unique genes after filtering out APA sites with low usage. We found that a total of 8831 APA sites were associated with at least one SNP with q-value < 0.05. The genomic distribution of lead APA SNPs indicated that the majority are intronic variants (33%), followed by downstream gene variants (26%), 3' UTR variants (17%), and upstream gene variants (within 1 kb region upstream of transcriptional start site, 10%). APA sites in 193 genes colocalized with GWAS data for at least one phenotype. Genes containing the top APA sites associated with GWAS variants include membrane associated ring-CH-type finger 2 (MARCHF2), nectin cell adhesion molecule 2 (NECTIN2), and butyrophilin subfamily 3 member A2 (BTN3A2). Overall, these findings suggest that APA may be an important mechanism for genetic variants in lung function and chronic obstructive pulmonary disease (COPD).
Language	English
Publishing date	2024-04-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddae055
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