A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program (preprint)

The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n=35) or hospitalization (n=42) due to severe COVID-19 using genome-wide association summary from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (nrs495828= 53 and nrs505922=59); strongest association with venous embolism, odds ratio (ORrs495828 1.33 (p=1.32 x 10-199), and thrombosis ORrs505922 1.33, p=2.2 x10-265. Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p=4.12 x 10-191; CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p=2.26x 10-12. The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p=6.48 x10-23, lupus OR 0.84, p=3.97 x 10-06. PheWAS stratified by genetic ancestry demonstrated differences in genotype-phenotype associations across ancestry. LMNA (rs581342) associated with neutropenia OR 1.29 p=4.1 x 10-13 among Veterans of African ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.

Work from Home Before and After the COVID-19 Outbreak (preprint)

Based on novel survey data, we document the evolution of commuting behavior in the U.S. over the course of the COVID-19 pandemic. Work from home (WFH) increased sharply and persistently after the outbreak, and much more so among some workers than others. Using theory and evidence, we argue that the observed heterogeneity in WFH transitions is consistent with potentially more permanent changes to work arrangements in some occupations, and not just temporary substitution in response to greater health risks. Consistent with increased WFH adoption, many more---especially higher-educated---workers expect to WFH in the future.

Employer Reallocation During the COVID-19 Pandemic: Validation and Application of a Do-It-Yourself CPS (preprint)

The Current Population Survey (CPS) is a central source of US labor market data. We show that, for a few thousand dollars, researchers can quickly design and implement their own online survey to supplement the CPS. The survey closely follows core features of the CPS, ensuring that outcomes are conceptually compatible and allowing researchers to weight and validate results using the official CPS. Yet the survey also allows for faster data collection, added flexibility, and novel questions. We show that the survey provided useful estimates of US labor market aggregates several weeks ahead of the CPS during the turbulent start of the COVID-19 recession. We then assess the extent of downward nominal wage rigidity at the onset of the pandemic, finding that wage reductions were widespread, but were more common for job switchers and recalled workers. We discuss a wide range of additional applications.

Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer (preprint)

Age is the dominant risk factor for infectious diseases, but the mechanisms linking the two are incompletely understood1,2. Age-related mosaic chromosomal alterations (mCAs) detected from blood-derived DNA genotyping, are structural somatic variants associated with aberrant leukocyte cell counts, hematological malignancy, and mortality3-11. Whether mCAs represent independent risk factors for infection is unknown. Here we use genome-wide genotyping of blood DNA to show that mCAs predispose to diverse infectious diseases. We analyzed mCAs from 767,891 individuals without hematological cancer at DNA acquisition across four countries. Expanded mCA (cell fraction >10%) prevalence approached 4% by 60 years of age and was associated with diverse incident infections, including sepsis, pneumonia, and coronavirus disease 2019 (COVID-19) hospitalization. A genome-wide association study of expanded mCAs identified 63 significant loci. Germline genetic alleles associated with expanded mCAs were enriched at transcriptional regulatory sites for immune cells. Our results link mCAs with impaired immunity and predisposition to infections. Furthermore, these findings may also have important implications for the ongoing COVID-19 pandemic, particularly in prioritizing individual preventive strategies and evaluating immunization responses.

Real-Time Labor Market Estimates During the 2020 Coronavirus Outbreak (preprint)

This project aims to provide labor market data several weeks ahead of official statistics via a national online labor market survey of a sample representative of the US working age population. We refer to the survey as the Real-Time Population Survey (RPS). Core questions in the RPS closely follow the official US labor market survey (the CPS), which allows us to construct estimates consistent with theirs. The RPS was conducted twice monthly from March through October, and since then is conducted monthly.