We develop novel statistical techniques for nonparametric Bayes analysis of high-dimensional covariate data, directly motivated by the largest population-based study ever conducted on the causes of birth defects. The methods we develop will enable borrowing of information and shrinkage across high-dimensional environmental, biomedical, pharmacological, and sociodemographic risk factors (and interactions among them) and across a multitude of birth defects, many of which are too rare to be studied in isolation. Using a hierarchical structure directly motivated by embryonic development, the borrowing of information can be informed by our knowledge of mechanistic development of the embryo. These novel methods may significantly impact the study of rare congenital malformations. The methods to be developed have broad application in public health and medicine, where exposures or characteristics of interest may be great in number and interactions are important, such as the examination high-dimensional gene by environment and gene-gene interactions.

Public Health Relevance

This project addresses a critical need of finding clues to the etiology and pathogenesis of congenital mal- formations, using data from the largest population-based study ever conducted on the causes of birth defects. While birth defects are the leading cause of infant mortality, the leading cause of death among children aged 1-4, and the fifth-ranked cause of premature mortality in the United States, many individual defects are too rare to be studied comprehensively, even in studies that are very large. Our new statistical methods for sparse shrinkage incorporate current knowledge of embryonic development and allow some borrowing of information across differ- ent birth defects while keeping each defect as a separate entity of interest in the statistical model. These novel methods will allow investigators to investigate the simultaneous influence of multiple exposures and combinations of exposures on multiple outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES020619-04
Application #
8685979
Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Dilworth, Caroline H
Project Start
2011-08-24
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$315,069
Indirect Cost
$52,792
Name
University of North Carolina Chapel Hill
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Davalos, Angel D; Luben, Thomas J; Herring, Amy H et al. (2017) Current approaches used in epidemiologic studies to examine short-term multipollutant air pollution exposures. Ann Epidemiol 27:145-153.e1
Johndrow, James E; Bhattacharya, Anirban; Dunson, David B (2017) TENSOR DECOMPOSITIONS AND SPARSE LOG-LINEAR MODELS. Ann Stat 45:1-38
Warren, Joshua L; Stingone, Jeanette A; Herring, Amy H et al. (2016) Bayesian multinomial probit modeling of daily windows of susceptibility for maternal PM2.5 exposure and congenital heart defects. Stat Med 35:2786-801
Buckley, Jessie P; Engel, Stephanie M; Braun, Joseph M et al. (2016) Prenatal Phthalate Exposures and Body Mass Index Among 4- to 7-Year-old Children: A Pooled Analysis. Epidemiology 27:449-58
Rappazzo, Kristen M; Warren, Joshua L; Meyer, Robert E et al. (2016) Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort. Birth Defects Res A Clin Mol Teratol 106:240-9
Zhou, Jing; Herring, Amy H; Bhattacharya, Anirban et al. (2016) Nonparametric Bayes modeling for case control studies with many predictors. Biometrics 72:184-92
Berchuck, Samuel I; Warren, Joshua L; Herring, Amy H et al. (2016) Spatially Modelling the Association Between Access to Recreational Facilities and Exercise: The 'Multi-Ethnic Study of Atherosclerosis'. J R Stat Soc Ser A Stat Soc 179:293-310
Buckley, Jessie P; Engel, Stephanie M; Mendez, Michelle A et al. (2016) Prenatal Phthalate Exposures and Childhood Fat Mass in a New York City Cohort. Environ Health Perspect 124:507-13
Nethery, Rachel C; Warren, Joshua L; Herring, Amy H et al. (2015) A common spatial factor analysis model for measured neighborhood-level characteristics: The Multi-Ethnic Study of Atherosclerosis. Health Place 36:35-46
Long, D Leann; Preisser, John S; Herring, Amy H et al. (2015) A Marginalized Zero-inflated Poisson Regression Model with Random Effects. J R Stat Soc Ser C Appl Stat 64:815-830

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