With public health genomics, SPH researchers are using 21^st century tools to tackle persistent, often age-old challenges to population health.

We use innovative statistical approaches and sequencing studies to identify new genomic variants that may lead to targeted screenings for disease risks. Our work is expanding the promise of precision medicine to population-wide health.

For example, by sequencing the exons — the protein-coding regions of the genome — our faculty recently discovered novel genes and mechanisms associated with increased risk for ischemic stroke. Another study found numerous places on the genome that differ between obese and non-obese individuals. These findings may one day be used to screen select populations to lower their risk of stroke and obesity.

We are committed to finding new prevention and treatment options to create better health.

Recently we collaborated on the largest epigenome-wide study of smoking, a global public health threat. Findings show that smoking alters particular gene pathways that could be theoretically “reset” to prevent or treat tobacco-related diseases. Other SPH faculty investigated genetic differences in drug metabolic pathways to find the most strategic use of an antiretroviral therapy drug to avoid premature discontinuation and associated morbidity.

Understanding disease processes is critical to enhancing public health and genomics can provide unique avenues toward that goal.

We know that psychiatric disorders have multiple genetic associations, but we need to know more about biological mechanisms. SPH faculty were part of a large study that found risk variants for schizophrenia, major depression, and bipolar disorder aggregate in particular biological pathways and that these pathways are frequently shared between disorders. This discovery suggests several new insights into the etiology of psychiatric disorders and can perhaps lead to better treatment options one day.

We are continuously exploring what the human genome can tell us — from how to live healthier lives to how long we might live — and we are finding ever-new ways to advance health for everyone.

(* asterisk marks SPH student, post-doc, or researcher at time of study)

• CYP2A6 genetic polymorphisms and biomarkers of tobacco smoke constituents in relation to risk of lung cancer in the Singapore Chinese Health Study. (Carcinogenesis). Jian-Min Yuan, Heather H. Nelson, et al. The uptake of tobacco carcinogens parallels the uptake of nicotine and cytochrome P450 2A6 (CYP2A6) is the primary enzyme responsible for nicotine metabolism. This study explored if genetic variation in CYP2A6 may affect smoking behavior and contribute to lung cancer risk.
• Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach.  (PLoS Medicine). Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, et al. The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. This study presents robust associations of BMI with differential DNA methylation at numerous loci in blood cells.
• Bayesian genome- and epigenome-wide association studies with gene level dependence. (Biometrics). Eric F. Lock, David B. Dunson. This study proposed a Bayesian approach for screening genetic and epigenetic data for associations with an observed phenotype in which the prior probability of an association for a given genomic variable depends on its gene, and the gene-specific probabilities are modeled nonparametrically.
• USAT: A Unifed Score-Based Association Test for Multiple Phenotype-Genotype Analysis. (Genetic Epidemiology). Debashree Ray*, James S. Pankow, Saonli Basu. This paper shows that multivariate analysis of variance (MANOVA) is generally very powerful for detecting genome-wide associations but there are situations, such as when a genetic variant is associated with all the traits, where MANOVA may not have any detection power.
• Epigenetic Signatures of Cigarette Smoking. (Circulation: Cardiovascular Genetics). Roby Joehanes, Allan C. Just, Riccardo E. Marioni, Luke C. Pilling… Weihau Guan… James S. Pankow… Ellen W. Demerath, et al. This study found that cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.

• Saonli Basu: 2013–2017, NIH, “Statistical methods for detection of genome-wide GxE interactions in longitudinal studies,” Principal Investigator
• Weihau Guan: 2016–2018, NIH NICHHD, “Offspring genome wide DNA methylation patterns at birth and the intrauterine environment in the EAGer Trial,” Co-Investigator
• Wei Pan: 2015–2019, NIH, “Genetic Association and Personalized Medicine,” Principal Investigator
• Jim Pankow: 2016–2017, UNC-Chapel Hill, “Genetic Epidemiology of Causal Variants Across the Life Course Phase II,” Principal Investigator
• Aaron Folsom: 2016–2017, Wake Forest University, “Obesity-related Epigenetic Changes and Type-2 Diabetes,” Principal Investigator

• Development and evaluation of genetic risk scores for childhood acute lymphoblastic leukemia (Epidemiology)
• Methods of Inference for Penalized Regression in High-Dimensional Genetic Association Studies (Biostatistics)
• Novel Tests for Detection of Gene-Environment Interaction (Biostatistics)