Comparative genome-wide association studies of a depressive symptom phenotype in a repeated measures setting by race/ethnicity in the multi-ethnic study of atherosclerosis. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Ware, Erin; Mukherjee, Bhramar; Sun, Yan; Diez-Roux, Ana; Kardia, Sharon; Smith, Jennifer
• Is Part Of: BMC genetics. Volume 16:Issue 1(2015)
• Page Start: 1
• Page End: 11
• Publication Date: 2015-12
• Subjects: Depressive symptoms -- Generalized estimating equations -- Genome-wide association studies -- Longitudinal -- Psychogenetics; Genetics -- Periodicals; 576.505
• DOI: 10.1186/s12863-015-0274-0
• Languages: English
• ISSNs: 1471-2156

Abstract

Abstract Background Time-varying phenotypes have been studied less frequently in the context of genome-wide analyses across ethnicities, particularly for mood disorders. This study uses genome-wide association studies of depressive symptoms in a longitudinal framework and across multiple ethnicities to find common variants for depressive symptoms. Ethnicity-specific GWAS for depressive symptoms were conducted using three approaches: a baseline measure, longitudinal measures averaged over time, and a repeated measures analysis. We then used meta-analysis to jointly analyze the results across ethnicities within the Multi-ethnic Study of Atherosclerosis (MESA, n = 6, 335), and then within ethnicity, across MESA and a sample from the Health and Retirement Study African- and European-Americans (HRS, n = 10, 163). Methods This study uses genome-wide association studies of depressive symptoms in a longitudinal framework and across multiple ethnicities to find common variants for depressive symptoms. Ethnicity-specific GWAS for depressive symptoms were conducted using three approaches: a baseline measure, longitudinal measures averaged over time, and a repeated measures analysis. We then used meta-analysis to jointly analyze the results across ethnicities within the Multi-ethnic Study of Atherosclerosis (MESA, n = 6, 335), and then within ethnicity, across MESA and a sample from the Health and Retirement Study African- and European-Americans (HRS, n = 10, 163). Results Several novel variants were identified at the genome-wide suggestive level (5×10−8 < p -value ≤ 5×10−6 ) in each ethnicity for each approach to analyzing depressive symptoms. The repeated measures analyses resulted in typically smaller p-values and an increase in the number of single-nucleotide polymorphisms (SNP) reaching genome-wide suggestive level. Conclusions For phenotypes that vary over time, the detection of genetic predictors may be enhanced by repeated measures analyses.