By Leslie Ridgeway

A research team co-led by USC Norris Comprehensive Cancer Center scientists is one of five teams to be awarded four-year grants totaling nearly $14 million to study the genomics of disease susceptibility in ethnically diverse populations. The National Institutes of Health (NIH) awarded the grant funds.

A team led by co-principal investigators Christopher Haiman, PhD, professor of preventive medicine, Keck School of Medicine of USC, and Loic Le Marchand, MD, PhD of the University of Hawaii, Honolulu, is scheduled to be awarded $3.1 million to examine the DNA from samples collected from the Multiethnic Cohort (MEC).

The research teams are receiving support — more than $3.8 million in fiscal year 2013 and nearly $14 million over four years — through the second round of the Population Architecture Using Genomics and Epidemiology (PAGE) program at the National Human Genome Research Institute (NHGRI), part of NIH. Haiman and Le Marchand were also NHGRI/PAGE awardees between 2008 and 2013. Other grant winners are from the University of North Carolina, Chapel Hill; Fred Hutchinson Cancer Research Center, Seattle; Mount Sinai School of Medicine, New York, N.Y.; and Rutgers University, New Brunswick, N.J.

“PAGE2 will be the first study that comprehensively investigates the contribution of less common and rare genetic variation in coding sequence in large numbers of samples from minority populations across a wide range of phenotypes and traits,” said Haiman. “We believe this project will shed light on the role of genetic variation in contributing to racial/ethnic health disparities for a number of chronic diseases including common cancers, type 2 diabetes, obesity, high blood glucose and other conditions.”

The team will use a novel and customized genotyping array specifically designed to interrogate functional coding variants in ethnic populations, Haiman said. The researchers plan to genotype approximately 50,000 samples from African, Hispanic and Asian ancestry for a wide range of diseases and traits.

“Dr. Haiman’s research is critically important to understanding disease disparities across populations for common cancers, and for many diseases that disproportionately affect minority populations,” said Stephen Gruber, MD, MPH, director, USC Norris Comprehensive Cancer Center. “We are grateful to the NIH for funding his work as part of the PAGE2 project.”

The MEC is a population-based study of more than 215,000 individuals ages 45 to 75 from California and Hawaii (which includes several racial/ethnic groups such as African-Americans, Japanese-Americans, Hispanic-Americans, Native Hawaiians and European-Americans) who are at varying risk for chronic diseases.

The PAGE2 projects are aimed at unraveling subtle variations in the genetic makeup among racial and ethnic groups that may account for differences in underlying risks for conditions such as high blood pressure and high blood lipids and common diseases such as cancer and heart disease.

“The goal of the PAGE program is to investigate ancestrally diverse populations to gain a better understanding of how genetic factors influence susceptibility to disease,” said epidemiologist Lucia Hindorff, PhD, PAGE program director at NHGRI.

Such factors include variations in genes called single nucleotide polymorphisms, or SNPs. These are tiny spelling changes in the DNA code that can affect a person’s risk of developing a disease or alter a response to medications. Over the years, research approaches called genome-wide association studies (GWAS) have led to the discovery of hundreds of gene variants associated with common diseases. The second phase of the PAGE program will focus on expanding the number of genetic variants analyzed to include variants that are more rare and likely to be functional.

To date, much of this research has focused on populations of European background. “We wanted the second group of grants to focus on non-European groups because many tend to have a higher burden of disease,” Hindorff said.

The grant numbers for the newly funded awards are the following: 1U01HG007416-01; 1U01HG007376-01; 1U01HG007397-01; 1U01HG007417-01; and 1U01HG007419-01.