Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE Network

Jennifer R. Malinowski, Joshua C. Denny, Suzette J Bielinski, Melissa A. Basford, Yuki Bradford, Peggy L. Peissig, David Carrell, David R. Crosslin, Jyotishman Pathak, Luke Rasmussen, Jennifer Pacheco, Abel Kho, Katherine M. Newton, Rongling Li, Iftikhar Jan Kullo, Christopher G. Chute, Rex L. Chisholm, Gail P. Jarvik, Eric B. Larson, Catherine A. McCarty & 5 others Daniel R. Masys, Dan M. Roden, Mariza De Andrade, Marylyn D. Ritchie, Dana C. Crawford

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article numbere111301
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 1 2014

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Electronic medical equipment
thyrotropin
Electronic Health Records
Thyrotropin
African Americans
Genomics
electronics
genomics
Genes
Serum
Genome-Wide Association Study
Single Nucleotide Polymorphism
thyroid diseases
Genome
Phenotype
multicultural diversity
phenotype
hypothyroidism
genome
Genetic Models

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE Network. / Malinowski, Jennifer R.; Denny, Joshua C.; Bielinski, Suzette J; Basford, Melissa A.; Bradford, Yuki; Peissig, Peggy L.; Carrell, David; Crosslin, David R.; Pathak, Jyotishman; Rasmussen, Luke; Pacheco, Jennifer; Kho, Abel; Newton, Katherine M.; Li, Rongling; Kullo, Iftikhar Jan; Chute, Christopher G.; Chisholm, Rex L.; Jarvik, Gail P.; Larson, Eric B.; McCarty, Catherine A.; Masys, Daniel R.; Roden, Dan M.; De Andrade, Mariza; Ritchie, Marylyn D.; Crawford, Dana C.

In: PLoS One, Vol. 9, No. 12, e111301, 01.12.2014.

Research output: Contribution to journalArticle

Malinowski, JR, Denny, JC, Bielinski, SJ, Basford, MA, Bradford, Y, Peissig, PL, Carrell, D, Crosslin, DR, Pathak, J, Rasmussen, L, Pacheco, J, Kho, A, Newton, KM, Li, R, Kullo, IJ, Chute, CG, Chisholm, RL, Jarvik, GP, Larson, EB, McCarty, CA, Masys, DR, Roden, DM, De Andrade, M, Ritchie, MD & Crawford, DC 2014, 'Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE Network', PLoS One, vol. 9, no. 12, e111301. https://doi.org/10.1371/journal.pone.0111301
Malinowski, Jennifer R. ; Denny, Joshua C. ; Bielinski, Suzette J ; Basford, Melissa A. ; Bradford, Yuki ; Peissig, Peggy L. ; Carrell, David ; Crosslin, David R. ; Pathak, Jyotishman ; Rasmussen, Luke ; Pacheco, Jennifer ; Kho, Abel ; Newton, Katherine M. ; Li, Rongling ; Kullo, Iftikhar Jan ; Chute, Christopher G. ; Chisholm, Rex L. ; Jarvik, Gail P. ; Larson, Eric B. ; McCarty, Catherine A. ; Masys, Daniel R. ; Roden, Dan M. ; De Andrade, Mariza ; Ritchie, Marylyn D. ; Crawford, Dana C. / Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE Network. In: PLoS One. 2014 ; Vol. 9, No. 12.
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abstract = "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.",
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AU - Malinowski, Jennifer R.

AU - Denny, Joshua C.

AU - Bielinski, Suzette J

AU - Basford, Melissa A.

AU - Bradford, Yuki

AU - Peissig, Peggy L.

AU - Carrell, David

AU - Crosslin, David R.

AU - Pathak, Jyotishman

AU - Rasmussen, Luke

AU - Pacheco, Jennifer

AU - Kho, Abel

AU - Newton, Katherine M.

AU - Li, Rongling

AU - Kullo, Iftikhar Jan

AU - Chute, Christopher G.

AU - Chisholm, Rex L.

AU - Jarvik, Gail P.

AU - Larson, Eric B.

AU - McCarty, Catherine A.

AU - Masys, Daniel R.

AU - Roden, Dan M.

AU - De Andrade, Mariza

AU - Ritchie, Marylyn D.

AU - Crawford, Dana C.

PY - 2014/12/1

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