Research Roundup: August 31, 2018

Welcome to the August 31, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Boning up on fracture risk

A new large-scale study reveals some of the genetic and clinical factors that raise the risk of bone fractures. Along with David Evans (University of Bristol and University of Queensland), Claes Ohlsson (Sahlgrenska Academy Institute of Medicine), J. Brent Richards (McGill University), and Fernando Rivadeneira (Erasmus University Medical Center), Broad associate member Douglas Kiel co-led the largest effort to date to uncover the genetics of osteoporosis and fracture risk. Reporting in the BMJ, the team conducted a genome-wide association study meta-analysis and found 15 genetic risk factors for bone fractures. The work suggests that treatments aimed at increasing bone strength may be more successful in preventing fractures than either supplementing with calcium and vitamin D or targeting other risk factors not found to mediate the disease, such as rheumatoid arthritis or diabetes.

Predicting the success of immunotherapy, computationally

Lack of adequate pre-treatment biomarkers makes it difficult to predict a patient’s response to immunotherapy. Previous research done in this field focused mainly on smaller sample sizes and specific tumor types. A team led by researchers at the Broad and Dana Farber Cancer Institute analyzed 249 pre-treatment tumors (from multiple cancer types) using whole-exome sequencing. Their analyses both validated existing biomarkers and revealed new genomic features of tumors that respond to immunotherapy, underlining the value of large-scale clinical data analysis for cancer therapy. Diana Miao, Claire Margolis, Natalie Vokes, and Broad Cancer Program associate member Eliezer Van Allen led the study, published in Nature Genetics. Learn more in GenomeWeb.

Breaking down neurodegeneration

A team including Stanley Center for Psychiatric Research group leader Joshua Levin and senior research associate Xian Adiconis, led by colleagues from Harvard Medical School and the Chinese Academy of Sciences, recently investigated the molecular links between aging and neurodegeneration. The team discovered that reduced Tak1 expression — normally lost over time in aging human brains — coupled with reduced expression of Tbk1, a gene linked to clinical neurodegeneration in humans, led to hallmark signs of neurodegeneration in mice. Experimental results indicated that both genes normally function in neurons to block the activity of RIPK1, a protein involved in neuroinflammation and cell death. The findings suggest that as RIPK1 stops being inhibited over time in aging brains, the tissue may be predisposed to degeneration. Get the full scoop in Cell and check out the Harvard news story.

To learn more about research conducted at the Broad, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.