Towards a phenome-wide catalog of human clinical traits impacted by genetic ancestry.

Logan Dumitrescu,Robert Goodloe,Dana C Crawford,Jonathan Boston,William S Bush,Sarah A Pendergrass,Nicole A Restrepo,Eric Farber-Eger

doi:10.1186/s13040-015-0068-y

Abstract

BackgroundRacial/ethnic differences for commonly measured clinical variables are well documented, and it has been postulated that population-specific genetic factors may play a role. The genetic heterogeneity of admixed populations, such as African Americans, provides a unique opportunity to identify genomic regions and variants associated with the clinical variability observed for diseases and traits across populations.MethodTo begin a systematic search for these population-specific genomic regions at the phenome-wide scale, we determined the relationship between global genetic ancestry, specifically European and African ancestry, and clinical variables measured in a population of African Americans from BioVU, Vanderbilt University’s biorepository linked to de-identified electronic medical records (EMRs) as part of the Epidemiologic Architecture using Genomics and Epidemiology (EAGLE) study. Through billing (ICD-9) codes, procedure codes, labs, and clinical notes, 36 common clinical and laboratory variables were mined from the EMR, including body mass index (BMI), kidney traits, lipid levels, blood pressure, and electrocardiographic measurements. A total of 15,863 DNA samples from non-European Americans were genotyped on the Illumina Metabochip containing ~200,000 variants, of which 11,166 were from African Americans. Tests of association were performed to examine associations between global ancestry and the phenotype of interest.ResultsIncreased European ancestry, and conversely decreased African ancestry, was most strongly correlated with an increase in QRS duration, consistent with previous observations that African Americans tend to have shorter a QRS duration compared with European Americans. Despite known racial/ethnic disparities in blood pressure, European and African ancestry was neither associated with diastolic nor systolic blood pressure measurements.ConclusionCollectively, these results suggest that this clinical population can be used to identify traits in which population differences may be due, in part, to population-specific genetics.Electronic supplementary materialThe online version of this article (doi:10.1186/s13040-015-0068-y) contains supplementary material, which is available to authorized users.

Highlights

Racial/ethnic differences for commonly measured clinical variables, such as cholesterol [1], body mass index [2], and hypertension [3], are well documented
We estimated global genetic ancestry in an admixed population and systematically searched for associations between European and African ancestry and clinical outcomes and traits mined from electronic medical records
We identified a significant association between European and African ancestry and QRS duration, and this association is supported by the known epidemiology of this electrocardiographic trait in diverse populations

Summary

Introduction

Racial/ethnic differences for commonly measured clinical variables, such as cholesterol [1], body mass index [2], and hypertension [3], are well documented. Previous studies have been primarily limited to genome-wide association studies (GWAS) stratified by race/ethnicity (self-reported and/or genetic ancestry) and admixture mapping studies of one or a handful of phenotypes in mostly epidemiologic collections Both GWAS and admixture mapping studies offer the opportunity to identify population-specific and trans-population associations involving specific genetic variants or genomic regions. Other previous studies have directly tested for associations between race/ethnicity or genetic ancestry and specific phenotypes such as atrial fibrillation [5,6,7] These latter studies offer the opportunity to identify and perhaps distinguish between genetic and cultural or environmental factors that may account for the differences in disease prevalence or incidence observed across populations. Racial/ethnic differences for commonly measured clinical variables are well documented, and it has been postulated that population-specific genetic factors may play a role. The genetic heterogeneity of admixed populations, such as African Americans, provides a unique opportunity to identify genomic regions and variants associated with the clinical variability observed for diseases and traits across populations

Methods

Results

Discussion

Conclusion