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

"This work was supported by Grants from the National Heart, Lung, and Blood Institute (NHLBI) (Contract Numbers 75N92019D00027, 75N92019D00028, 75N92019D00029 and 75N92019D00030) and previous Grants (R01HL090863, R01HL109315, R01HL109301, R01HL109284, R01HL109282, and R01HL109319 and cooperative agreements: U01HL41642, U01HL41652, U01HL41654, U01HL65520 and U01HL65521); by the National Institute of Environmental Health Sciences (Grant Numbers R01ES021367, R01ES025216, P42ES033719, P30ES009089), by ANID-Millennium Science Initiative Program-No NCS2021_013-SocioMed (ALRC), by the Maria Zambrano grant N degrees ZA21063 for the requalification of the Spanish university system-NextGeneration EU (ALRC) and by a fellowship from ""la Caixa"" Foundation (ID 100010434) (fellowship code ""LCF/BQ/DR19/11740016"") (ADR). The funders had no role in the planning, conducting, analysis, interpretation, or writing of this study. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (United States) or the National Health Institute Carlos III (Spain).

Este trabajo fue apoyado por subvenciones del Instituto Nacional del Corazón, los Pulmones y la Sangre (NHLBI) (números de contrato 75N92019D00027, 75N92019D00028, 75N92019D00029 y 75N92019D00030) y subvenciones anteriores (R01HL090863, R01HL109315, 109301, R01HL109284, R01HL109282 y R01HL109319 y acuerdos de cooperación: U01HL41642, U01HL41652, U01HL41654, U01HL65520 y U01HL65521); por el Instituto Nacional de Ciencias de la Salud Ambiental (Becas Números R01ES021367, R01ES025216, P42ES033719, P30ES009089), por ANID-Programa Iniciativa Científica Milenio-No NCS2021_013-SocioMed (ALRC), por la beca María Zambrano N grados ZA21063 para la recualificación de españoles sistema universitario-NextGeneration EU (ALRC) y por una beca de la Fundación ""la Caixa"" (ID 100010434) (código de beca ""LCF/BQ/DR19/11740016"") (ADR). Los financiadores no tuvieron ningún papel en la planificación, realización, análisis, interpretación o redacción de este estudio. El contenido de este manuscrito es responsabilidad exclusiva de los autores y no representa necesariamente las opiniones oficiales de los Institutos Nacionales de Salud (Estados Unidos) o del Instituto Nacional de Salud Carlos III (España)."

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

Biología Molecular

Genética y Herencia

Sistema Respiratorio

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