A genome-wide study of DNA methylation in white blood cells and asthma in Latino children and youth

ABSTRACT

Latinos are heavily affected with childhood asthma. Little is known about epigenetic mechanisms of asthma in Latino youth. We conducted a meta-analysis of two epigenome-wide association studies (EWAS) of asthma, using DNA from white blood cells (WBCs) from 1,136 Latino children and youth aged 6 to 20 years. Genes near the top CpG sites in this EWAS were examined in a pathway enrichment analysis, and we then assessed whether our results replicated those from publicly available data from three independent EWAS conducted in non-Latino populations. We found that DNA methylation profiles differed between subjects with and without asthma. After adjustment for covariates and multiple testing, two CpGs were differentially methylated at a false discovery rate (FDR)-adjusted P < 0.1, and 193 CpG sites were differentially methylated at FDR-adjusted P < 0.2. The two top CpGs are near genes relevant to inflammatory signalling, including CAMK1D (Calcium/Calmodulin Dependent Protein Kinase ID) and TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains). Moreover, 25 genomic regions were differentially methylated between subjects with and without asthma, at Šidák-corrected P < 0.10. An enrichment analysis then identified the TGF-beta pathway as most relevant to asthma in our analysis, and we replicated some of the top signals from publicly available EWAS datasets in non-Hispanic populations. In conclusion, we have identified novel epigenetic markers of asthma in WBCs from Latino children and youth, while also replicating previous results from studies conducted in non-Latinos.

KEYWORDS:

• Asthma
• epigenome-wide
• DNA methylation
• white blood cells

Acknowledgments

The authors thank the children, youth, and families who participated in the PR-GOAL, EVA-PR, and GALA II studies. The authors thank all study collaborators in GALA II: Shannon Thyne, UCSF; Harold J. Farber, Texas Children’s Hospital; Denise Serebrisky, Jacobi Medical Centre; Rajesh Kumar, Lurie Children’s Hospital of Chicago; Emerita Brigino-Buenaventura, Kaiser Permanente; Michael A. LeNoir, Bay Area Paediatrics; Kelley Meade, Children’s Hospital, Oakland; William Rodriguez-Cintron, VA Hospital, Puerto Rico; Pedro C. Avila, Northwestern University. The authors thank the health care providers and community clinics who participated and supported GALA II. In particular, the authors thank study coordinator Sandra Salazar; the recruiters who obtained the data: Duanny Alva, MD, Gaby Ayala-Rodriguez, Lisa Caine, Elizabeth Castellanos, Jaime Colon, Denise DeJesus, Blanca Lopez, Brenda Lopez, MD, Louis Martos, Vivian Medina, Juana Olivo, Mario Peralta, Esther Pomares, MD, Jihan Quraishi, Johanna Rodriguez, Shahdad Saeedi, Dean Soto, and Ana Taveras.

Disclosure statement

Dr. Celedon has received research materials from GSK and Merck (inhaled steroids) and Pharmavite (vitamin D and placebo capsules) in order to provide medications free of cost to participants in NIH-funded studies, unrelated to the current work. The other authors report no conflicts of interest.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

The Puerto Rico Genetics of Obesity, Asthma, and Lifestyle (PR-GOAL) study and the Epigenetic Variation of childhood Asthma in Puerto Ricans (EVA-PR) study were supported by grants HL079966, HL117191 and MD011764 from the U.S. National Institutes of Health (NIH), and by The Heinz Endowments (PI: J.C.C.). The Genes-Environments and Admixture in Latino Americans (GALA II) Study and E.G.B were supported by the Sandler Family Foundation, the American Asthma Foundation, the RWJF Amos Medical Faculty Development Program, the Harry Wm. and Diana V. Hind Distinguished Professor in Pharmaceutical Sciences II, the National Heart, Lung, and Blood Institute (NHLBI) [R01HL117004, R01HL128439, R01HL135156, X01HL134589]; the National Institute of Environmental Health Sciences [R01ES015794, R21ES24844]; the National Institute on Minority Health and Health Disparities (NIMHD) [P60MD006902, R01MD010443, RL5GM118984] and the Tobacco-Related Disease Research Program [24RT-0025].