Microglia have emerged as important players in brain aging and pathology. To understand how genetic risk for neurological and psychiatric disorders is related to microglial function, large transcriptome studies are essential. Here, we describe the transcriptome analysis of 255 primary human microglia samples isolated at autopsy from multiple brain regions of 100 human subjects. We performed systematic analyses to investigate various aspects of microglial heterogeneities, including brain region and aging. We mapped expression and splicing quantitative trait loci and showed that many neurological disease susceptibility loci are mediated through gene expression or splicing in microglia. Fine-mapping of these loci nominated candidate causal variants that are within microglia-specific enhancers, finding associations with microglia expression of USP6NL for Alzheimer’s disease and P2RY12 for Parkinson’s disease. We have built the most comprehensive catalog to date of genetic effects on the microglia transcriptome and propose candidate functional variants in neurological and psychiatric disorders.

2020). A characterization of the molecular phenotype and inflammatory response of schizophrenia patient-derived microglia-like cells. Brain behavior and immunity, 90, 196-207.

Background The COVID‐19 pandemic is an ongoing global health threat, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Questions remain about how SARS‐CoV‐2 impacts pregnant individuals and their children. Objective To expand our understanding of the effects of SARS‐CoV‐2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology, by using serological tests to measure IgG antibody levels. Methods The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant individuals receiving obstetrical care at the Mount Sinai Healthcare System from 20 April 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before 22 September 2020. For each woman, we tested the latest prenatal blood sample available to establish seropositivity using a SARS‐CoV‐2 serologic enzyme‐linked immunosorbent assay. Additionally, RT‐PCR testing was performed on a nasopharyngeal swab taken during labour. Pregnancy outcomes of interest (i.e., gestational age at delivery, preterm birth, small for gestational age, Apgar scores, maternal and neonatal intensive care unit admission, and length of neonatal hospital stay) and covariates were extracted from medical records. Excluding individuals who tested RT‐PCR positive at delivery, we conducted crude and adjusted regression models to compare antibody positive with antibody negative individuals at delivery. We stratified analyses by race/ethnicity to examine potential effect modification. Results The SARS‐CoV‐2 seroprevalence based on IgG measurement was 16.4% (95% confidence interval 13.7, 19.3; n=116). Twelve individuals (1.7%) were SARS‐CoV‐2 RT‐PCR positive at delivery. Seropositive individuals were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre‐pregnancy BMI compared with seronegative individuals. None of the examined pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity. Conclusion Seropositivity for SARS‐CoV‐2 without RT‐PCR positivity at delivery (suggesting that infection occurred earlier during pregnancy) was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample from New York City.

Microglial cells have emerged as potential key players in brain aging and pathology. To capture the heterogeneity of microglia across ages and regions, and to understand how genetic risk for neurological and psychiatric brain disorders is related to microglial function, large transcriptome studies are essential. Here, we describe the transcriptome analysis of 255 primary human microglia samples isolated at autopsy from multiple brain regions of 100 human subjects. We performed systematic analyses to investigate various aspects of microglial heterogeneities, including brain region, age and sex. We mapped expression and splicing quantitative trait loci and showed that many neurological disease susceptibility loci are mediated through gene expression or splicing in microglia. Fine-mapping of these loci nominated candidate causal variants that are within microglia-specific enhancers, including novel associations with microglia expression of USP6NL for Alzheimer′s disease, and P2RY12 for Parkinson′s disease. In summary, we have built the most comprehensive catalog to date of genetic effects on the microglia transcriptome and propose molecular mechanisms of action of candidate functional variants in several neurological and psychiatric diseases.

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