Dataset Information

An Examination of the Relationship between Lipid Levels and Associated Genetic Markers across Racial/Ethnic Populations in the Multi-Ethnic Study of Atherosclerosis.

ABSTRACT: Large genome-wide association studies have reported hundreds of genetic markers associated with lipid levels. However, the discovery and estimated effect of variants at these loci, derived from samples of exclusively European descent, may not generalize to the majority of the world populations. We examined the collective strength of association among these loci in a diverse set of U.S. populations from the Multi-Ethnic Study of Atherosclerosis. We constructed a genetic risk score for each lipid outcome based on previously identified lipid-associated genetic markers, and examined the relationship between the genetic risk scores and corresponding outcomes. We discover this relationship was often moderated by race/ethnicity. Our findings provide insight into the generalizability and predictive utility of large sample size meta-analyses results when leveraging data from a single population. We hope these findings will encourage researchers to investigate genetic susceptibility in more diverse populations and explore the source of such discrepancies. Until then, we caution clinicians, genetic counselors, and genetic testing consumers when interpreting genetic data on complex traits.

SUBMITTER: Johnson L

PROVIDER: S-EPMC4423846 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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An Examination of the Relationship between Lipid Levels and Associated Genetic Markers across Racial/Ethnic Populations in the Multi-Ethnic Study of Atherosclerosis.

Johnson Lucia L Zhu Jonathan J Scott Erick R ER Wineinger Nathan E NE

PloS one 20150507 5

Large genome-wide association studies have reported hundreds of genetic markers associated with lipid levels. However, the discovery and estimated effect of variants at these loci, derived from samples of exclusively European descent, may not generalize to the majority of the world populations. We examined the collective strength of association among these loci in a diverse set of U.S. populations from the Multi-Ethnic Study of Atherosclerosis. We constructed a genetic risk score for each lipid ...[more]

PMID: 25951326

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Project description:BackgroundAlthough left ventricular cardiac geometric indices such as size and sphericity characterize adverse remodeling and have prognostic value in symptomatic patients, little is known of shape distributions in subclinical populations. We sought to quantify shape variation across a large number of asymptomatic volunteers, and examine differences among sub-cohorts.MethodsAn atlas was constructed comprising 1,991 cardiovascular magnetic resonance (CMR) cases contributed from the Multi-Ethnic Study of Atherosclerosis baseline examination. A mathematical model describing regional wall motion and shape was used to establish a coordinate map registered to the cardiac anatomy. The model was automatically customized to left ventricular contours and anatomical landmarks, corrected for breath-hold mis-registration between image slices. Mathematical techniques were used to characterize global shape distributions, after removal of translations, rotations, and scale due to height. Differences were quantified among ethnicity, sex, smoking, hypertension and diabetes sub-cohorts.ResultsThe atlas construction process yielded accurate representations of global shape (errors between manual and automatic surface points in 244 validation cases were less than the image pixel size). After correction for height, the dominant shape component was associated with heart size, explaining 32% of the total shape variance at end-diastole and 29% at end-systole. After size, the second dominant shape component was sphericity at end-diastole (13%), and concentricity at end-systole (10%). The resulting shape components distinguished differences due to ethnicity and risk factors with greater statistical power than traditional mass and volume indices.ConclusionsWe have quantified the dominant components of global shape variation in the adult asymptomatic population. The data and results are available at cardiacatlas.org. Shape distributions were principally explained by size, sphericity and concentricity, which are known correlates of adverse outcomes. Atlas-based global shape analysis provides a powerful method for quantifying left ventricular shape differences in asymptomatic populations.Trial registrationClinicalTrials.gov NCT00005487.

Dataset Information

An Examination of the Relationship between Lipid Levels and Associated Genetic Markers across Racial/Ethnic Populations in the Multi-Ethnic Study of Atherosclerosis.

Publications

An Examination of the Relationship between Lipid Levels and Associated Genetic Markers across Racial/Ethnic Populations in the Multi-Ethnic Study of Atherosclerosis.

Similar Datasets

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