Hair follicle gene expression profiling in the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS)

Kristina L Buschur; Molly Martorella; Renee Garcia-Flores; Benjamin M Smith; Marcello Ziosi; Igor Barjaktarevic; Eugene R Bleecker; Stephanie A Christenson; Alejandro P Comellas; Gerard J Criner; Mark T Dransfield; Nadia N Hansel; Robert J Kaner; Jerry A Krishnan; Deborah A Meyers; Elizabeth C Oelsner; Victor E Ortega; Robert Paine III; Prescott G Woodruff; R Graham Barr; Tuuli Lappalainen

doi:10.1186/s12920-025-02270-w

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Hair follicle gene expression profiling in the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS)

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Hair follicle gene expression profiling in the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS)

Kristina L Buschur, Molly Martorella, Renee Garcia-Flores, Benjamin M Smith, Marcello Ziosi, Igor Barjaktarevic, Eugene R Bleecker, Stephanie A Christenson, Alejandro P Comellas, Gerard J Criner, …

BMC medical genomics, Vol.18(1), 192

12/09/2025

DOI: 10.1186/s12920-025-02270-w

PMCID: PMC12690836

PMID: 41366429

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https://doi.org/10.1186/s12920-025-02270-wView

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Abstract

Transcriptomic analysis is common in large cohort studies but is generally restricted to cells in blood, which limits inferences about organs of interest, and direct organ sampling is mostly infeasible in large cohorts. New techniques for RNA-seq from noninvasive biosamples may provide the opportunity to profile transcriptomes of additional tissues for more organ-relevant insights at scale. We investigated the feasibility and utility of hair follicle gene expression profiling in a multi-center study of chronic obstructive pulmonary disease (COPD). Bulk RNA-seq was performed on hair follicles collected in the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS), a multi-center longitudinal study of COPD (n = 97). The resulting hair follicle gene expression data were characterized and compared both to gene expression in whole blood and bronchial epithelium previously measured in SPIROMICS and to Genotype-Tissue Expression (GTEx) project tissue gene expression by principal component analysis and single-sample gene enrichment analysis, used to estimate hair follicle cell type proportions, and tested for association with disease-relevant lung phenotypes. eQTL discovery was also performed and colocalization with a genome-wide association study for lung function was tested. Hair follicles reliably produced transcriptomic data of sufficient quality and number for cell type composition, which revealed mostly epithelial and fibroblast cells. Comparison to other tissues previously profiled in SPIROMICS and GTEx project demonstrated transcriptomes from hair follicles were much more similar to those from lung parenchyma than blood. Combining these data with rich clinical, imaging, and genomic profiling in SPIROMICS, we found that they provided an attractive approach for discovery of associations with complex lung phenotypes, particularly of the airways. Finally, we investigated hair follicle genetic architecture through expression quantitative trait locus (eQTL) discovery and demonstrated better colocalization with lung-related genetic associations than blood. Here, we demonstrated that RNA-seq applied to hair follicle transcriptomic profiling can be scaled up successfully in a multi-center study to yield inferences not available from blood transcriptomics.

Aged

Female

Gene Expression Profiling

Genome-Wide Association Study

Hair Follicle - metabolism

Humans

Longitudinal Studies

Male

Middle Aged

Pulmonary Disease, Chronic Obstructive - genetics

Pulmonary Disease, Chronic Obstructive - pathology

Quantitative Trait Loci

Transcriptome

Details

Title: Subtitle: Hair follicle gene expression profiling in the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS)
Creators: Kristina L Buschur - Columbia University Irving Medical Center
Molly Martorella - New York Genome Center
Renee Garcia-Flores - New York Genome Center
Benjamin M Smith - Columbia University Irving Medical Center
Marcello Ziosi - New York Genome Center
Igor Barjaktarevic - University of California, Los Angeles
Eugene R Bleecker - University of Arizona
Stephanie A Christenson - University of California, San Francisco
Alejandro P Comellas - University of Iowa
Gerard J Criner - Temple University
Mark T Dransfield - University of Alabama at Birmingham
Nadia N Hansel - Johns Hopkins University
Robert J Kaner - Weill Cornell Medicine
Jerry A Krishnan - University of Illinois Urbana-Champaign
Deborah A Meyers - University of Arizona
Elizabeth C Oelsner - Columbia University Irving Medical Center
Victor E Ortega - Mayo Clinic Hospital
Robert Paine III - University of Utah
Prescott G Woodruff - University of California, San Francisco
R Graham Barr - Columbia University
Tuuli Lappalainen - KTH Royal Institute of Technology
Resource Type: Journal article
Publication Details: BMC medical genomics, Vol.18(1), 192
DOI: 10.1186/s12920-025-02270-w
PMID: 41366429
PMCID: PMC12690836
NLM abbreviation: BMC Med Genomics
ISSN: 1755-8794
eISSN: 1755-8794
Publisher: Springer Nature
Grant note: HHSN268200900017C / NHLBI NIH HHS HHSN268200900016C / NHLBI NIH HHS HHSN268200900019C / NHLBI NIH HHS HHSN268200900020C / NHLBI NIH HHS U24 HL141762 / NHLBI NIH HHS HHSN268200900018C / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS HHSN268200900014C / NHLBI NIH HHS HHSN268200900015C / NHLBI NIH HHS HHSN268200900013C / NHLBI NIH HHS
Language: English
Date published: 12/09/2025
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
Record Identifier: 9985091811702771

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