Comparing self-reported ethnicity to genetic background measures in the context of the Multi-Ethnic Study of Atherosclerosis (MESA)

Four clusters are identified using 96 ancestry informative markers. Three of these clusters are well delineated, but 30% of the self-reported Hispanic-Americans are misclassified. We also found that MESA SRE provides type I error rates that are consistent with the nominal levels. More extensive simulations revealed that this finding is likely due to the multi-ethnic nature of the MESA. Finally, we describe situations where SRE may perform as well as a GBMA in controlling the effect of population stratification and admixture in association tests.The performance of SRE as a control variable in genetic association tests is more nuanced than previously thought, and may have more value than it is currently credited with, especially when smaller replication studies are being considered in multi-ethnic samples.The use of self-reported race and ethnicity (SRE) in genetic and epidemiologic studies has been much discussed in the literature [1-8]. Some researchers proposed to completely ban their utilization in these studies claiming that race and ethnicity are poorly defined social constructs with weak biologic and genetic basis [2,3,9]. Others, however, have argued that completely disregarding racial and ethnic differences in genetic and epidemiologic studies may not be appropriate, since these differences can be useful when generating and exploring new hypotheses regarding the effect of environmental and genetic risk factors and their interaction on important medical outcomes [1,9].Some studies have found SRE to be closely related to an individual's genetically estimated ancestry proportions [8,10] and have suggested that SRE may provide adequate control against type I error inflation and/or loss of power due to population stratification and admixture in genetic association tests. However, it has also been shown [5,11] that while SRE may be sufficient to predict the continent or subcontinent on which an individual's ancestors were born, genetic markers may provide a finer g