Genetic Variants Associated with Serum Thyroid Stimulating Hormone (TSH) Levels in European Americans and African Americans from the eMERGE Network
| Autor: | Christopher G. Chute, Dan M. Roden, Peggy L. Peissig, Dana C. Crawford, Abel N. Kho, David Carrell, Rex L. Chisholm, Mariza de Andrade, Joshua C. Denny, Rongling Li, David R. Crosslin, Yuki Bradford, Luke V. Rasmussen, Catherine A. McCarty, Jyotishman Pathak, Marylyn D. Ritchie, Jennifer A. Pacheco, Daniel R. Masys, Gail P. Jarvik, Iftikhar J. Kullo, Jennifer Malinowski, Eric B. Larson, Katherine M. Newton, Suzette J. Bielinski, Melissa A. Basford |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
endocrine system diseases Epidemiology lcsh:Medicine Thyrotropin Genome-wide association study Body Mass Index Database and Informatics Methods Endocrinology Medicine and Health Sciences Electronic Health Records Euthyroid Statistical Analysis of Genetic Association lcsh:Science Aged 80 and over Multidisciplinary Thyroid disease Middle Aged 3. Good health Europe Female Quantitative Trait Association Studies Research Article medicine.medical_specialty endocrine system Single-nucleotide polymorphism Research and Analysis Methods Polymorphism Single Nucleotide White People Thyroid-stimulating hormone Internal medicine Genetic model Computational Techniques medicine Genome-Wide Association Studies Genetics Humans Genetic Association Studies Genetic association Aged business.industry lcsh:R Biology and Life Sciences Computational Biology Human Genetics medicine.disease Genome Analysis Thyroid Diseases Black or African American Africa lcsh:Q business FOXE1 Genome-Wide Association Study |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 12, p e111301 (2014) |
| ISSN: | 1932-6203 |
| Popis: | Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10-17, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10-6, β = -0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = -0.09), VEGFA (rs11755845 p = 0.01, β = -0.13), and NFIA (rs334699 p = 1.50×10-3, β = -0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more diverse populations. |
| Databáze: | OpenAIRE |
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