Data from: Genetic ancestry and population differences in levels of inflammatory cytokines in women: role for evolutionary selection and environmental factors

Background: Selection pressure due to exposure to infectious pathogens endemic to Africa may explain distinct genetic variations in immune response genes. However, the impact of those genetic variations on human immunity remains understudied, especially within the context of modern lifestyles and living environments, which are drastically different from early humans in sub Saharan Africa. There are few data on population differences in constitutional immune environment, where genetic ancestry and environment are likely two primary sources of variation. Methods and Findings: In a study integrating genetic, molecular and epidemiological data, we examined population differences in plasma levels of 14 cytokines involved in innate and adaptive immunity, including those implicated in chronic inflammation, and possible contributing factors to such differences, in 914 AA and 855 EA women. We observed significant differences in 7 cytokines, including higher plasma levels of CCL2, CCL11, IL4 and IL10 in EAs and higher levels of IL1RA and IFNα2 in AAs. Analyses of a wide range of demographic and lifestyle factors showed significant impact, with age, education level, obesity, smoking, and alcohol intake, accounting for some, but not all, observed population differences for the cytokines examined. Levels of two pro-inflammatory chemokines, CCL2 and CCL11, were strongly associated with percent of African ancestry among AAs. The signal was pinpointed through admixture mapping to local ancestry at 1q23, with fine-mapping analysis refined to the Duffy-null allele of rs2814778. In AA women, this variant was a major determinant of systemic levels of CCL2 (p=1.1e-58) and CCL11 (p=2.2e-110), accounting for 19% and 40% of the phenotypic variance, respectively. Conclusion: Our data reveal strong ancestral footprints in inflammatory chemokine regulation. The Duffy-null allele may indicate a loss of the buffering function for chemokine levels. The substantial immune differences by ancestry may have broad implications to health disparities between AA and EA populations. cytokine.data.amber.05042018This dataset contains 14 cytokines measured using plasma samples from a total of 1,769 women enrolled as controls in the Women’s Circle of Health Study (WCHS) and the Carolina Breast Cancer Study (CBCS). This study is a part of the African American Breast Cancer Etiology and Risk (AMBER) consortium.