Repositorio
Institucional

Domingo-Relloso, Arce,

Riffo-Campos, Angela L.

Powers, Martha

Tellez-Plaza, Maria

Haack, Karin

Brown, Robert H.

Umans, Jason G.

Fallin, M. Daniele

Cole, Shelley A.

Navas-Acien, Ana

Sanchez, Tiffany R.

An epigenome-wide study of DNA methylation profiles and lung function among American Indians in the Strong Heart Study

BMC

CLINICAL EPIGENETICS

en

Background Epigenetic modifications, including DNA methylation (DNAm), are often related to environmental exposures, and are increasingly recognized as key processes in the pathogenesis of chronic lung disease. American Indian communities have a high burden of lung disease compared to the national average. The objective of this study was to investigate the association of DNAm and lung function in the Strong Heart Study (SHS). We conducted a cross-sectional study of American Indian adults, 45-74 years of age who participated in the SHS. DNAm was measured using the Illumina Infinium Human MethylationEPIC platform at baseline (1989-1991). Lung function was measured via spirometry, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), at visit 2 (1993-1995). Airflow limitation was defined as FEV1 < 70% predicted and FEV1/FVC < 0.7, restriction was defined as FEV1/FVC > 0.7 and FVC < 80% predicted, and normal spirometry was defined as FEV1/FVC > 0.7, FEV1 > 70% predicted, FVC > 80% predicted. We used elastic-net models to select relevant CpGs for lung function and spirometry-defined lung disease. We also conducted bioinformatic analyses to evaluate the biological plausibility of the findings. Results Among 1677 participants, 21.2% had spirometry-defined airflow limitation and 13.6% had spirometry-defined restrictive pattern lung function. Elastic-net models selected 1118 Differentially Methylated Positions (DMPs) as predictors of airflow limitation and 1385 for restrictive pattern lung function. A total of 12 DMPs overlapped between airflow limitation and restrictive pattern. EGFR, MAPK1 and PRPF8 genes were the most connected nodes in the protein-protein interaction network. Many of the DMPs targeted genes with biological roles related to lung function such as protein kinases. Conclusion We found multiple differentially methylated CpG sites associated with chronic lung disease. These signals could contribute to better understand molecular mechanisms involved in lung disease, as assessed systemically, as well as to identify patterns that could be useful for diagnostic purposes. Further experimental and longitudinal studies are needed to assess whether DNA methylation has a causal role in lung disease.

artículo original

10.1186/s13148-022-01294-8

PDF

DNA methylation

Lung function

Lung disease

Epigenetics

American Indians

ADAPTIVE ELASTIC-NET

DISEASE

ASSOCIATION

FIBROSIS

PACKAGE

MODELS

LGL1

Oncología

Genética y herencia

Metilación del ADN

Función pulmonar

Enfermedad pulmonar

Epigenética

Indios americanos

RED ELÁSTICA ADAPTATIVA

ENFERMEDAD

ASOCIACIÓN

FIBROSIS

PAQUETE

MODELOS

LGL1

An epigenome-wide study of DNA methylation profiles and lung function among American Indians in the Strong Heart Study

artículo original

version publicada

CC BY 4.0

CC BY 4.0

acceso abierto

acceso abierto

WOS:000809035300003

ANID NCS2021_013

NHLBI 75N92019D00027

NHLBI 75N92019D00028

NHLBI 75N92019D00029

NHLBI 75N92019D00030

NHLBI R01HL090863

NHLBI R01HL109315

NHLBI R01HL109301

NHLBI R01HL109284

NHLBI R01HL109282

NHLBI R01HL109319

NHLBI U01HL41642

NHLBI U01HL41652

NHLBI U01HL41654

NHLBI U01HL65520

NHLBI U01HL65521

NIHES R01ES021367

NIHES R01ES025216

NIHES P42ES033719

NIHES P30ES009089

CAIXA 00010434, LCF/BQ/DR19/11740016

UR ZA21063