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PNAS Papers on Woodrat Microbiome, Maternal Cannabis Use, Gene-Based Testing

Editor's Note: Some of the articles described below are not yet available at the PNAS site but are scheduled to be posted this week.

A team from the US and Mexico looks at ties between the gut microbiome and features such as diet, geography, host genetics, and neutral processes like passive dispersal and ecological drift in herbivorous woodrats from seven Neotoma species and more than two dozen wild populations from the southwestern US, along with wild-caught woodrats moved into captive settings. With metabarcoding-based sequencing on microbiome and dietary plant samples, the researchers tracked the effects of host phylogeny and other factors on the gut microbiome, uncovering species-specific gut microbial shifts in captive woodrats. "Although diet and geography influenced natural microbiome structure, the effects of host phylogeny were stronger for both wild and captive animals," they report, adding that the host genetic influence tended to become more pronounced in captivity, while dietary effects waned.

Maternal cannabis use during pregnancy appears to coincide with altered immune-related gene expression in the placenta at birth as well as elevated levels of hair cortisol, anxiety- and hyperactivity-related behaviors, and heart rate variability in three to six-year-old children resulting from the pregnancies, according to another paper in PNAS. Using placental RNA sequencing, behavioral surveys, hair hormone testing, and other approaches, investigators at Icahn School of Medicine at Mount Sinai and City University of New York followed more than 300 mother-child pairs over time, comparing results for children born to 71 mothers who used cannabis during pregnancy and 251 non-users. "Overall," they write, "our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood."

A Columbia University-led team describes a gene-based testing strategy called GeneScan3DKnock that relies on chromatin immunoprecipitation sequencing-based long-range chromatin interaction profiles, gene region-based testing, and a statistical knockoff genotype method. "Through simulations and applications to genome-wide association studies (GWAS) and whole-genome sequencing data for multiple diseases and traits, we show that the proposed test increases the power over state-of-the-art gene-based tests in the literature, identifies genes that replicate in larger studies, and can provide a more narrow focus on the possible causal genes at a locus by reducing the confounding effect of linkage disequilibrium," the authors write, adding that "incorporating genetic variation in distal regulatory elements tends to improve power over conventional tests."