Method Developed by BUSPH Alumna Used in Major Genetic Study.

A new study of genetic variants that used a statistical method developed by a BUSPH graduate has found six novel genetic loci involved in insulin resistance.

Alisa Manning, a recent graduate of the biostatistics PhD program, is the first author of the study, which appears in Nature Genetics. The co-authors, who come from dozens of institutions, used a method Manning developed as part of her PhD thesis to identify genetic variants influencing fasting glycemic traits and insulin resistance. The findings help to further characterize the etiology of Type 2 diabetes (T2D) and the role of insulin resistance in the process.

The research team hypothesized that genes implicated in insulin-resistance pathways could be uncovered by accounting for differences in body mass index (BMI) and potential interaction between BMI and the genetic variants. The team used a novel “joint meta-analysis approach” developed by Manning to test associations with fasting insulin and glucose.

The approach “enabled us to simultaneously test both the genetic main effect, adjusted for BMI, and potential interaction between each genetic variant and BMI,” the research team said. “This joint meta-analysis (JMA) approach can provide increased power for detecting the genetic loci when underlying interaction effects are suspected but unknown.”

The team, which included Josée Dupuis, a professor of biostatistics who had worked with Manning, said its approach was successful in revealing loci implicated in insulin resistance in numbers proportional to those implicated in insulin secretion.

“Our results underline the importance of taking (obesity) into account to understand the heterogeneity of T2D etiology,” the researchers said.

Manning graduated from BUSPH in May 2011 and is currently a postdoctoral research fellow at the Broad Institute in Cambridge.

submitted by: Lisa Chedekel

chedekel@bu.edu