BA1 - Ancestry association analyses of WHI traits

Investigator Names and Contact Information

Michael Seldin (mfseldin@ucdavis.edu)

Introduction/Intent

The proposed studies will examine whether a proportion of variation in specific health measurements and outcomes in the Women’s Health Initiative (WHI) can be explained by genetic variation attributable to ancestry. Our study will distinguish ethnicity-outcome relationships due to ancestrally determined genetic variation differ from associations due to other (non-genetic) correlates of ethnicity, such as socioeconomic status. Characterization of study subjects using a panel of ancestrally informative markers (AIMs) is a novel feature of the proposed study and includes the use of an informative marker set of SNPs for examining European substructure in the “White” subset of subjects. For the two admixed populations in WHI (Black and Hispanic) the study will focus on several discrete disease measurements including breast cancer, CHD, stroke, and hip fractures and the quantitative measurement of bone mineral density. For bone mineral density the studies also includes an admixture mapping study to identify specific chromosomal regions that can explain ancestry linkage. For the White population the study will focus on signs and measurements of osteoporosis by examining subjects with hip fractures, and the quantitative trait, bone mineral density. In this aspect of the study we will also examine response to interventional strategies within WHI.

Our goal for this project is to determine whether specific WHI outcomes are associated with ancestry due to genetic factors. Several categories of potential risk factors will be examined, including demographic (age, geography), socioeconomic (e.g., education, income, occupational history and insurance status), and lifestyle factors (e.g., exposure to tobacco smoke). The AIMs information is a unique feature of this study and will be particularly valuable for distinguishing between ethnic differences in outcome due to ancestrally determined genetic variation from other causes, such as socioeconomic or other potential confounding factors. We will employ a number of statistical methods for data analysis, including MCMC methods, logistic regression and multivariate methods. The large size of the study population, wealth of potentially important predictors, and plans to examine interactions among determinants will significantly expand our understanding of the determinants of multiple outcomes and represent major study strengths. The proposal is divided into three focused AIMs outlined in Figure below.

Aim 1: To determine whether the relative contribution of continental ancestry is linked to specific baseline traits and outcomes in two admixed population groups within the WHI study: Black (African American) and Hispanic subjects.

Aim 2: To define the relationship between European population substructure and predictive phenotypes for osteoporosis and whether outcome intervention strategies differ in subpopulations within the “White” population.

Aim 3: Admixture Mapping of Bone Mineral Density within the “Black” population.

Results/Findings

Some of the publications related to this ancillary study are: 964, 1185, 1253, 1315.
For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Papers section of this website.