AS422 - Cardiovascular biomarkers in WHI Native Americans

Investigator Names and Contact Information

Charles Kooperberg (clk@fredhutch.org)

Introduction/Intent

This page provides study documentation for AS422. For description of the specimen results, see Specimen Results Description (open to public). Data sets of the specimen results are included in the existing WHI datasets located on the WHI Data on this site (sign in and a completed Data Distribution Agreement are required; see details on the Data site).

Within WHI are almost 600 women who identified themselves as American Indians/Native Americans based on Form 2-Eligibility Screening, and whose consent status allows for the submission of genetic data to dbGaP. While not a large number of participants relative to other ancestral groups in WHI, compared to other cohorts this is still a number that is of some interest, given that most cohorts included almost no Native Americans.

In the PAGE consortium (WHI study M6), there was great enthusiasm when we genotyped 500 of the Native Americans on the MetaboChip, with the plan to include them in multi-ethnic analyses. For the extension of PAGE (PAGE-2) we have included all of these 600 participants in the planned ExomeChip genotyping for the WHI-PAGE2 proposal that is currently under review. As expected for any minority sample, these Native Americans are likely admixed and the MetaboChip data will be interesting from that perspective. Having access to these data will also offer the opportunity to learn more about this rarely studied ancestral group, especially as we can compare them with Hispanics, who have a substantial Native American admixture component.

This number of Native Americans does not allow any ancestral specific analysis of specific clinical outcomes. However, for continuous biomarkers, the results would be of more interest given the increased power of continuous traits and the fact that we would limit analyses to generalization of findings from other ancestral groups rather than large scale discovery of novel loci specific to Native Americans. The higher rates of obesity, diabetes, and cardiovascular disease among Native Americans makes metabolic and cardiovascular biomarkers of particular interest in this group.

For the 594 Native Americans, 353 in the OS and 241 in the CT, we propose that WHI measure the panel of eight metabolic and cardiovascular biomarkers: low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, total cholesterol, glucose, insulin, creatinine, and C-reactive protein (CRP)​. The results of these biomarkers would be available to the larger WHI community as well as to the larger research community via dbGaP. We imagine that in many studies where these biomarkers are studied, this will allow for Native Americans to function as a validation study to see whether results found in other ethnicities generalize to Native Americans.

As mentioned above, within the WHI-PAGE study we would be excited to include these Native Americans in our analyses of the MetaboChip data and, if we get the WHI-PAGE2 grant, ExomeChip data. But we believe that the use of this data is much larger than just PAGE.