Skip to main content
Premium Trial:

Request an Annual Quote

Nature Studies on Genetic Components of Complex Traits, Cytosine Base Editor, More

Biobanks represent valuable resources for identifying the genetic components of complex traits, including rare variants, but high computational costs limit the ability of existing methods to account for confounders such as population stratification and sample relatedness. To address this issue, scientists from the University of Michigan School of Public Health have developed a method — called SAIGE-GENE — for region-based association analysis that is capable of handling very large samples while inferring and accounting for sample relatedness. As reported in Nature Genetics, SAIGE-GENE is demonstrated through an analysis of nearly 70,000 samples from the Nord-Trøndelag Health Study and more than 400,000 samples from the UK Biobank, identifying potentially novel association signals. "By providing a scalable solution to the current largest and future even larger datasets, our method will contribute to identifying trait-susceptibility rare variants and elucidating the genetic architecture of complex traits," the authors write.

A novel cytosine base editor (CBE) with reduced DNA and RNA off-targeting is described in Nature Methods this week. By screening a number of rationally engineered CBEs, a Chinese Academy of Sciences-led team finds that mutation residues in predicted DNA-binding sites can dramatically decrease the Cas9-independent off-target effects. Further, they identify one CBE variant that retains high on-target editing efficiency but with extremely low off-target and bystander edits. The findings, the study's authors write, point to the potential of CBEs in biomedicine.

A genome-wide association study combining standard and subtype-specific analyses in breast cancer is reported in Nature Genetics this week. The work identifies nearly three dozen novel susceptibility loci for the disease and provides an improved understanding of genetic predisposition to breast cancer subtypes. Members of the Breast Cancer Association Consortium performed a GWAS — featuring 133,384 breast cancer cases and 113,789 controls, along with 18,908 BRCA1 mutation carriers of European ancestry — using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status, as well as tumor grade. They find 32 novel susceptibility loci, 15 of which showed evidence for associations with at least one tumor feature. Other findings include five loci showing associations in opposite directions between luminal and non-luminal subtypes and which contained cell-specific enhancers that differed between normal luminal and basal mammary cells.