Annual Review of Genomics and Human Genetics - Early Publication

Genomics has the potential to transform human health, biomedical research, and life sciences by providing deep insights into genetic variation and disease mechanisms. However, fully realizing these benefits requires a well-trained workforce equipped to handle, analyze, and interpret increasingly complex genomic and linked datasets. The rapid evolution of sequencing technologies, machine learning, and data science tools has heightened the demand for professionals proficient in bioinformatics, high-performance computing, and genomic data governance. This review presents a global perspective on workforce development in genomic data science, detailing key competencies necessary for both research and clinical applications. We discuss some of the existing training programs, competency frameworks, and regional approaches to skills development while identifying gaps in education, infrastructure, and accessibility. Additionally, we explore the integration of genomic data science into healthcare, addressing challenges such as equitable access to training and the need for cross-disciplinary expertise. Tackling these challenges is essential for cultivating a diverse, skilled workforce capable of driving advancements in genomic research, precision medicine, and public health.

Social and behavioral scientists increasingly work with geneticists or adapt the methods of genetic research to investigate genomic variation in a wide variety of behavioral and social phenotypes. Using genome-wide association studies, these social and behavioral genomics (SBG) researchers generate polygenic indexes (PGIs)—weighted sums of the estimated effects of each genetic variant on an individual's phenotype. This review examines the ethical, conceptual, and social issues in SBG research and its downstream applications. In particular, it focuses on PGIs for ethically sensitive SBG phenotypes—those that (a) can be viewed as consequential to social status (e.g., obesity and substance-use disorders), (b) are contributing or have historically contributed to harmful stereotypes about minoritized groups and threaten to reify the biologization of social identities (e.g., financial prowess and athleticism), and/or (c) are central to a minoritized group's identity (e.g., sexual orientation and sexual behavior).

Genetic variation is a major determinant of drug response across populations. Owing to advances in sequencing technologies over the last two decades, several clinically actionable variants or haplotypes have been characterized in genes that encode proteins mediating drug pharmacokinetics or pharmacodynamics. Therefore, clinical application of pharmacogenomics has gained significant traction as a promising tool for enabling drug therapy optimization to mitigate adverse drug reactions while promoting drug efficacy. However, the implementation of pharmacogenetics testing has been slow in African settings and other resource-limited global regions. Moreover, there is a need to address gaps in various pharmacogenomics knowledgebases, especially regarding the genetic diversity in underrepresented populations. It is also important to ensure that emerging assays and technologies do not heighten existing healthcare disparities affecting African populations. We present the status of pharmacogenomics in Africa, highlighting its potential to impact health outcomes in the safe and efficacious use of medicines.

Newborn screening for phenylketonuria began in the United States in the early 1960s, and it expanded one disease at a time until the development of tandem mass spectrometry. This technology allowed for screening many conditions simultaneously, but its uneven adoption led to wide disparities. A collaboration between the American College of Medical Genetics and Genomics and the US Health Resources and Services Administration resulted in a recommended uniform screening panel. Newborn sequencing (NBSeq) identifies many monogenic disorders, although to date it cannot identify all cases identified by tandem mass spectrometry. NBSeq has the potential to reduce diagnostic odysseys and increase health equity, but it could also exacerbate disparities and cause psychosocial and clinical harms due to overdiagnosis, oversurveillance, and/or overtreatment. By expanding beyond previously established public health screening principles, NBSeq also challenges the mandatory nature of current screening. In this review, we examine the promise and perils of NBSeq.

In this short memoir, I recount the series of improbable interactions and events that led me from medical school to a leadership role in the Human Genome Project.