Five research teams have received new four-year awards to study the genomics of disease susceptibility in ethnically diverse populations. The projects aim to unravel the subtle variations in genetic makeup among groups – including African-Americans, Asian-Americans, Hispanics and more – that may account for differences in risks for conditions such as high blood pressure and high blood lipids, in addition to common diseases such as cancer and heart disease.
These research teams are receiving support – more than $3.8 million in fiscal year 2013, and nearly $14 million over four years, based on the availability of funds – through the Population Architecture Using Genomics and Epidemiology (PAGE) program of the National Human Genome Research Institute (NHGRI), part of NIH. The current grantees are the second group of researchers to be funded through the PAGE program.
"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, Ph.D., PAGE program director at NHGRI.
Such factors include variations 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, a research approach called a genome-wide association study (GWAS) has led to the discovery of hundreds of gene variants associated with common diseases. This next phase of the PAGE program will focus on expanding the number of genetic variants analyzed to include those that are more rare and likely to be functional. Scientists hope that these common and rare genetic variants will allow them to piece together the complex biological picture of many diseases and lead to more personalized prevention, diagnoses and treatment.
To date, much of this research – including the initial round of PAGE grants – has focused on whites. The new round of grants supports studies on groups of more diversified heritages.
"We wanted the second group of grants to focus on non-whites because many tend to have a greater incidence of disease," said Dr. Hindorff. For example, African-Americans, Hispanics and Native Americans tend to have a higher incidence of high blood pressure and obesity, along with accompanying heart disease and risk of stroke compared to whites.
"There are often population-related biological pathways that contribute to disease, so looking at many traits and diseases together gives a more complete picture of the role of genetic variation," she said. "All of the funded studies take advantage of large epidemiological studies and datasets."
The following groups have been awarded grants (pending available funds):
Dr. North and her colleagues collaborate in a program called CALiCo II, or Genetic Epidemiology of Causal Variants Across the Life Course Phase II. The partnership focuses on population-based studies aimed at uncovering potential connections between genetic variants and complex diseases and conditions, such as heart disease, type 2 diabetes, obesity and hypertension. The scientists will analyze the DNA collected from several of these large studies involving many Hispanic and African American participants to pinpoint rare variants that might play roles in these diseases and conditions.
The researchers will focus on minority populations to try to better understand the impact of rare variants on the development of common diseases such as diabetes, heart disease and cancer, and conditions such as inflammation, high glucose, insulin resistance and abnormal lipid levels. They plan to study rare gene variations found in the genome's protein-coding regions and their association with these conditions and diseases in African-Americans, Hispanics and Native Americans.
To do this, the team will study participants from the Women's Health Initiative (WHI), a long-term national health study focused on strategies for chronic disease prevention. The scientists will compare the DNA of the WHI subjects to the DNA sequences of approximately 350,000 rare gene variants that are associated with these diseases and conditions. The scientists hope that identifying new genome locations and variants associated with disease susceptibility may provide new clues to disease development and help in screening and drug discovery.
Drs. Haiman, Marchand and their co-workers will examine the DNA from samples collected from the Multiethnic Cohort (MEC), 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, Hispanics, Native Hawaiians and whites who are at varying risk for chronic diseases. They will study gene variants linked to a wide range of diseases and conditions, such as type 2 diabetes, obesity, common cancers, fasting insulin levels, high blood glucose and high lipids. The researchers hope they will uncover new gene variant-disease associations, and that their findings will enable them to build models to understand disease risks in these diverse groups.
Dr. Loos and her colleagues will examine data from approximately 29,000 participants of the Mount Sinai BioMe Biobank, an ongoing resource based on electronic medical records from several ethnically diverse communities in New York City. The researchers aim to gain a greater understanding of the underlying causes of differences in disease incidence in these communities by studying the differences in genetic make-up in these groups that contribute to metabolic, heart, and kidney disorders. The new insights are expected to improve treatment of at-risk populations and may lead to reductions in health disparities among underserved minority populations.
The PAGE coordinating center will serve as a centralized resource to help organize and manage research study logistics, as well as data gathering and analyses, and to facilitate collaborations. The coordinating center team includes statistical, population and molecular geneticists, genetic epidemiologists, computer and information scientists and biostatisticians. It will also serve as a data clearinghouse for results.
The grant numbers for the newly funded awards are the following: 1U01HG007416-01; 1U01HG007376-01; 1U01HG007397-01; 1U01HG007417-01; and 1U01HG007419-01.
NHGRI is one of the 27 institutes and centers at the National Institutes of Health. The NHGRI Extramural Research Program supports grants for research and training and career development at sites nationwide. Additional information about NHGRI can be found at http://www.genome.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
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