From public health genomics to precision public health: a 20-year journey.

In this paper, we review the evolution of the field of public health genomics in the United States in the past two decades. Public health genomics focuses on effective and responsible translation of genomic science into population health benefits. We discuss the relationship of the field to the core public health functions and essential services, review its evidentiary foundation, and provide examples of current US public health priorities and applications. We cite examples of publications to illustrate how Genetics in Medicine reflected the evolution of the field. We also reflect on how public-health genomics is contributing to the emergence of "precision public health" with near-term opportunities offered by the US Precision Medicine (AllofUs) Initiative.

A pilot study of host genetic variants associated with influenza-associated deaths among children and young adults.

We compared the prevalence of 8 polymorphisms in the tumor necrosis factor and mannose-binding lectin genes among 105 children and young adults with fatal influenza with US population estimates and determined in subanalyses whether these polymorphisms were associated with sudden death and bacterial co-infection among persons with fatal influenza. No differences were observed in genotype prevalence or minor allele frequencies between persons with fatal influenza and the reference sample. Fatal cases with low-producing MBL2 genotypes had a 7-fold increased risk for invasive methicillin-resistant Staphylococcus aureus (MRSA) co-infection compared with fatal cases with high- and intermediate-producing MBL2 genotypes (odds ratio 7.1, 95% confidence interval 1.6-32.1). Limited analysis of 2 genes important to the innate immune response found no association between genetic variants and fatal influenza infection. Among children and young adults who died of influenza, low-producing MBL2 genotypes may have increased risk for MRSA co-infection.

Use of family history in clinical guidelines for diabetes and colorectal cancer.

BACKGROUND: Family history is a risk factor for many chronic diseases and as such is often incorporated into clinical practice guidelines. PURPOSE: To assess the consistency of the use of family history in selected guidelines for colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) and to examine how these definitions influence their screening recommendations. METHODS: Using a web-based search, guidelines issued between 2001 and 2011 from Australia, Canada, the United Kingdom, the U.S., and the WHO were reviewed. In total, 21 guidelines were found that included family history information (14 for CRC and seven for T2DM). For each guideline, the definition of family history and the way this definition influenced screening recommendations was recorded. Analyses were completed on May 2011. RESULTS: Family history was defined most often as the presence of affected first-degree relatives; the number of such relatives and their ages at diagnosis were considered sometimes in making specific recommendations. The definition of family history and its impact on recommendations varied substantially, even for the same disease. CONCLUSIONS: Despite the importance of family history as a risk factor for CRC and T2DM, its use in screening recommendations is inconsistent among guidelines from major organizations; however, differences do not appear large enough to prevent achieving consensus among the guidelines for each disease. More standardized recommendations for use of family history in CRC and T2DM screening guidelines could enhance their utility for prevention.

A population approach to precision medicine.

The term P4 medicine is used to denote an evolving field of medicine that uses systems biology approaches and information technologies to enhance wellness rather than just treat disease. Its four components include predictive, preventive, personalized, and participatory medicine. In the current paper, it is argued that in order to fulfill the promise of P4 medicine, a "fifth P" must be integrated-the population perspective-into each of the other four components. A population perspective integrates predictive medicine into the ecologic model of health; applies principles of population screening to preventive medicine; uses evidence-based practice to personalize medicine; and grounds participatory medicine on the three core functions of public health: assessment, policy development, and assurance. Population sciences-including epidemiology; behavioral, social, and communication sciences; and health economics, implementation science, and outcomes research-are needed to show the value of P4 medicine. Balanced strategies that implement both population- and individual-level interventions can best maximize health benefits, minimize harm, and avoid unnecessary healthcare costs.

ADRB2 Arg16Gly polymorphism, lung function, and mortality: results from the Atherosclerosis Risk in Communities study.

BACKGROUND: Growing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy. We sought to examine the association of beta-agonist use and the Arg16Gly polymorphism with lung function and mortality among participants in the Atherosclerosis Risk in Communities study. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped study participants and analyzed the association of the Arg16Gly polymorphism and beta-agonist use with lung function at baseline and clinical examination three years later and with all-cause mortality during 10 years of follow-up. Lung function was characterized by percent-predicted forced expiratory volume in 1 second. Associations were examined separately for blacks and whites. Black beta-agonist users with the Arg/Arg genotype had better lung function at baseline and at the second clinical visit than those with Arg/Gly and Gly/Gly genotypes. Adjusted mean percent-predicted FEV(1) was 21% higher in Arg/Arg subjects compared to Gly/Gly at baseline (p = 0.01) and 20% higher than Gly/Gly at visit 2 (p = 0.01). Arg/Gly subjects had adjusted percent-predicted FEV(1) 17% lower than Arg/Arg at baseline but were similar to Arg/Arg subjects at visit 2. Although black beta-agonist users with the Arg/Arg genotype appeared to have better crude survival rates, the association between genotype and all-cause mortality was inconclusive. We found no difference in lung function or mortality by genotype among blacks who did not use beta-agonists or among whites, regardless of beta-agonist use. CONCLUSIONS: Black beta-agonist users with the ADRB2 Arg16Arg genotype had better lung function, and, possibly, better overall survival compared to black beta-agonist users with the Gly16Gly genotype. Our findings highlight the need for additional studies of sufficient size and statistical power to allow examination of outcomes among beta-agonist users of different races and genotypes.