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Supplemental Data Supplemental Data include 2 figures, 13 tables, and additional funding information and can be found with this article online at http://dx.doi.org/10.1016/j.ajhg.2016.05.003. Supplemental Data Document S1. Figures S1 and S2, Tables S3–S5, S7, S8, and S10–S12, and Additional Funding Information Download Table S1. Information on Genotyping Methods, Quality Control of SNPs, and Statistical Analyses for Exomechip Study Download Table S2. Description and Design of Studies Participating in the Blood-Cell Consortium with White Blood Cell Trait Data Download Table S6. List of All White Blood Cell Trait Loci that Reached Exome-wide Significance in the Discovery Meta-analysis Stage Download Table S9. Comparison of Allele Frequencies and Directions of Effect across Ancestries of White Blood Cell Trait Loci Download Table S13. Expression Quantitative Trait Loci Lookups of White Blood Cell Trait Variants Identified in the Present Study Download Document S2. Article plus Supplemental Data Download Web Resources 1000 Genomes, http://www.1000genomes.org BCX ExomeChip association results, http://www.mhi-humangenetics.org/en/resources CheckVCF, https://github.com/zhanxw/checkVCF GRASP, http://grasp.nhlbi.nih.gov/Overview.aspx HPC @ NIH, http://hpc.nih.gov OMIM, http://www.omim.org/ R statistical software, http://www.r-project.org/ RareMETALS, http://genome.sph.umich.edu/wiki/RareMETALS RareMetalWorker, http://genome.sph.umich.edu/wiki/RAREMETALWORKER RvTests, http://genome.sph.umich.edu/wiki/RvTests White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3′ UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.

Background: There is a lack of nationally representative prospective data on the impact of the COVID-19 pandemic on diabetes care and management in adults with type 2 diabetes. We examined changes in diabetes care and management practices before and after the onset of the COVID-19 pandemic., Methods: Using the National Health Interview Survey, we analyzed data from 870 adults living with type 2 diabetes who were interviewed in 2019 and re-interviewed between August and December 2020. Exposure to the COVID-19 pandemic was defined by year of survey (2019, pre-pandemic; 2020, pandemic). We estimated percent change in past year blood sugar check by a health professional and current use of blood sugar lowering medication overall and by sociodemographic subgroups., Results: Receiving an annual blood sugar test fell by -3.3 percentage points (pp) (95% CI -5.7, -1.0), from 98.3% in 2019 to 95.0% in late 2020. The reduction in annual blood glucose testing was largely consistent across socio-demographic groups and was particularly pronounced among adults not working and adults aged 65 years and older. In the same time period, current use of diabetes medications increased by +3.8 pp (0.7, 6.9), from 85.9% to 89.7%. The increase in medication use was most pronounced among individuals aged 40-64-year old, employed, and those living in large central metropolitan areas., Conclusions: Nationally, adults with Type 2 diabetes reported a reduction in annual blood glucose testing by a health professional and an increase in diabetes medication usage during the COVID-19 pandemic. If sustained after the end of the COVID-19 public health emergency, these changes have implications for national diabetes management and care., Competing Interests: Conflict of interest The authors declare that there are no relevant conflicts of interest.