Haixiang Zhang1, Yinan Zheng2, Zhou Zhang2, Tao Gao2, Brian Joyce2, Grace Yoon3, Wei Zhang2, Joel Schwartz4, Allan Just5, Elena Colicino4, Pantel Vokonas6, Lihui Zhao2, Jinchi Lv7, Andrea Baccarelli4, Lifang Hou2, Lei Liu2. 1. Center for Applied Mathematics, Tianjin University, Tianjin 300072, China. 2. Department of Preventive Medicine. 3. Department of Statistics, Northwestern University, Chicago, IL 60611, USA. 4. Department of Environmental Health, Harvard University, Boston, MA 02115, USA. 5. Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 6. Veterans Affairs Boston Healthcare System and Boston University School of Medicine, VA Normative Aging Study, Boston, MA 02118, USA. 7. Data Sciences and Operations Department, University of Southern California, Los Angeles, CA 90089, USA.
Abstract
MOTIVATION: High-dimensional DNA methylation markers may mediate pathways linking environmental exposures with health outcomes. However, there is a lack of analytical methods to identify significant mediators for high-dimensional mediation analysis. RESULTS: Based on sure independent screening and minimax concave penalty techniques, we use a joint significance test for mediation effect. We demonstrate its practical performance using Monte Carlo simulation studies and apply this method to investigate the extent to which DNA methylation markers mediate the causal pathway from smoking to reduced lung function in the Normative Aging Study. We identify 2 CpGs with significant mediation effects. AVAILABILITY AND IMPLEMENTATION: R package, source code, and simulation study are available at https://github.com/YinanZheng/HIMA CONTACT: lei.liu@northwestern.edu.
MOTIVATION: High-dimensional DNA methylation markers may mediate pathways linking environmental exposures with health outcomes. However, there is a lack of analytical methods to identify significant mediators for high-dimensional mediation analysis. RESULTS: Based on sure independent screening and minimax concave penalty techniques, we use a joint significance test for mediation effect. We demonstrate its practical performance using Monte Carlo simulation studies and apply this method to investigate the extent to which DNA methylation markers mediate the causal pathway from smoking to reduced lung function in the Normative Aging Study. We identify 2 CpGs with significant mediation effects. AVAILABILITY AND IMPLEMENTATION: R package, source code, and simulation study are available at https://github.com/YinanZheng/HIMA CONTACT: lei.liu@northwestern.edu.
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