Research Roundup: July 23, 2021

Linking obesity genetics to mechanism, relating SARS-CoV-2 viral load and symptoms, and an -omic view on IBD treatment

Broad Communications
Credit: Broad Communications

Welcome to the July 23, 2021 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Mechanisms underlying the strongest genetic association with obesity 

Noncoding variants near the FTO gene are linked to obesity, but the underlying mechanisms are unclear. Building on their previous Variant-to-Function work at the FTO obesity risk locus, a team including Samantha Laber, Sara Forcisi (Helmholtz Zentrum München), Hans Hauner (Technical University of Munich), institute member Melina Claussnitzer in the Metabolism Program, and Roger Cox (MRC Harwell Institute) studied the effects of one of these variants, rs1421085, in an engineered mouse model. Their results support a context-dependent role of the variant in adipose depots and reveal its effects on obesity-related whole-body phenotypes. The team also used untargeted high-resolution metabolome analysis to show that the variant mediates cross-species conserved changes in steroid patterns after nutritional challenges in humans and mice. Read more in Science Advances.

Surveying viral loads in nursing homes

Asymptomatic infections contribute to SARS-CoV-2 spread, but the relative viral loads in patients with and without symptoms are unknown. Institute scientist Niall Lennon of the Genomics Platform, associate member Roby Bhattacharyya of the Infectious Disease and Microbiome Program, president and founding director (on leave) Eric Lander, institute scientist and senior director of the Genomics Platform Stacey Gabriel, and colleagues used RT-qPCR to study viral loads in nearly 33,000 residents and staff in assisted living facilities and nursing homes. They found similar viral load distributions in symptomatic and asymptomatic cohorts, potentially suggesting transmission risk may also be similar. Most patients were asymptomatic when they tested positive, indicating that RT-qPCR can be used to detect SARS-CoV-2 in asymptomatic patients, which may be key for future surveillance testing. Learn more in the Journal of Infectious Diseases and a Broad blog post.

Multi-omic markers of IBD treatment response

Response to treatment for inflammatory bowel disease (IBD) is difficult to predict because of the complex intestinal microbiome and lack of predictive biomarkers. Visiting scientist Jonathan Wei Jie Lee, group leader Damian Plichta, core institute member Ramnik Xavier of the Infectious Disease and Microbiome Program and colleagues profiled stool and blood samples from patients with IBD before treatment and then tracked treatment response. They used modeling and machine learning to identify metagenomic, metabolomic and proteomic markers that could predict which patients would achieve remission. Biomarkers varied by therapy class, with microbial diversity in the gut being a strong indicator of anti-cytokine therapy success. These response markers could lead to better IBD treatment selection. Read more in Cell Host and Microbe.

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