UC Davis researchers will conduct a first-of-its-kind genetic study to determine the importance of ancestry on the development of diseases in women, thanks to a grant of nearly $1.4 million from the National Heart, Lung, and Blood Institute. Researchers will be analyzing samples taken from more than 160,000 postmenopausal women who participated in the 15-year Women's Health Initiative study, which focused on strategies for preventing heart disease, breast and colorectal cancer and osteoporosis fractures -- the most frequent causes of death and poor quality of life in postmenopausal women.

UC Davis was one of 40 sites across the nation that began enrolling women in 1993 for the historic WHI study. More than 4,000 women aged 50 to 70 from the Sacramento region participated at UC Davis over the years. Now, UC Davis is one of 12 institutions nationwide to receive a two-year WHI contract to study genetic and biological markers of disease in postmenopausal women.


"This research allows us to identify additional genes that are important in causing diseases that disproportionately affect women or affect them in different ways than men," explained Michael Seldin, principal investigator and chair of the Rowe Program in Human Genetics at UC Davis.

The sheer number and diversity of the women who took part in the WHI study will also allow Seldin and his colleagues to determine the impact of ancestry on disease-risk.

"If we know who is at higher risk, we can individualize our approaches to screening and prevention," said Seldin, who is also professor of biochemistry and medicine.

In the UC Davis study, Seldin and his colleagues will use samples taken from WHI participants and determine part of each woman's genotype, or genetic fingerprint, using high through-put assays that specifically examine ancestry. They will then correlate this genetic information with phenotypic data -- the presence or absence of disease traits. They will also look for associations between genetic data, observed disease status and ancestry.

The first part of the study will involve women who self-identified as African-American or Hispanic. Since individuals in these groups are often of mixed ancestry, Seldin and his colleagues will determine their continental ancestry -- the percent of their genetic make-up that can be attributed to African, European or East Asian ancestry. They will then look to see which diseases correlate with ancestry.

Seldin will also be comparing women of African-American or European ancestry to pinpoint the location of genes associated with decreased bone mineral density, a measure of osteoporosis.

"It is well-known that bone mineral density is higher in individuals with a higher percentage of African descent. But, women of African-American descent also get osteoporosis. Including them in the analysis will enhance our ability to find the genes we are looking for," he said.

The study will also look at a subset of women identified as being of European descent to determine whether European ancestry puts women at higher risk of hip fracture. Seldin's previous work found that European populations actually represent two genetically distinct Southern and Northern groups.

According to Seldin, the WHI contracts will allow researchers to get the most out of the original WHI study, which has already provided practical information to women and their physicians about the health benefits of hormone therapy, dietary patterns, calcium/vitamin supplementation on preventing heart disease, cancer and osteoporosis.

"It's a huge resource that promises to help us identify genes important in human disease so that we can work out the basic biochemical and biological basis for disease," he said. "This is a unique opportunity to ask additional questions."

Co-investigators include John Robbins, UC Davis professor of medicine; and Lihong Qi, assistant professor in the Rowe Program in Human Genetics.