NDLI: A genetic risk score for thyroid peroxidase antibodies associates with clinical thyroid disease in community-based populations.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chaker, Layal Daya, Natalie Völzke, Henry Hofman, Albert Selvin, Elizabeth Li, Yong Schultheiss, Ulla T. Medici, Marco Uitterlinden, Andre G. Teumer, Alexander Peeters, Robin P. Homuth, Georg Nauck, Matthias Köttgen, Anna
Description	Author Affiliation: Schultheiss UT ( Renal Division (U.T.S., Y.L., A.K.), Department of Medicine IV, Medical Center, University of Freiburg, 79106 Freiburg, Germany)
Abstract	CONTEXT: Antibodies against thyroid peroxidase (TPOAbs) are detected in 90% of all patients with Hashimoto thyroiditis, the most common cause of hypothyroidism. Hypothyroidism is associated with a range of adverse outcomes. The current knowledge of its genetic underpinnings is limited. OBJECTIVE: The purpose of this study was to identify novel genetic variants associated with TPOAb concentrations and positivity using genome-wide association data and to characterize their association with thyroid function and disease. DESIGN, SETTING, AND PARTICIPANTS: We studied European ancestry participants of 3 independent prospective population-based studies: Atherosclerosis Risk In Communities study (n = 7524), Study of Health in Pomerania (n = 3803), and Study of Health in Pomerania-TREND (n = 887). EXPOSURE: Single nucleotide polymorphisms (SNPs), individually and combined into a genetic risk score (GRS), were examined. MAIN OUTCOMES: The main outcomes were TPOAb concentrations and positivity, thyroid hormone concentrations (TSH, free T4), and clinical thyroid diseases (subclinical and overt hypothyroidism and goiter). RESULTS: Significantly associated single nucleotide polymorphisms (P < 5 · 10(-8)) mapped into 4 genomic regions not previously implicated for TPOAbs (RERE, extended HLA region) and into 5 previously described loci. A higher Genetic Risk Score (GRS) based on these 9 SNPs showed strong and graded associations with higher TPOAb, TSH, and lower free T4 concentrations (P < .001). Compared with individuals in the lowest GRS quartile, those in the highest quartile had 1.80-fold higher odds of subclinical hypothyroidism (95% confidence interval, 1.27-2.55) and 1.89-fold higher odds of overt hypothyroidism (95% confidence interval, 1.24-2.87). CONCLUSION: The identification of 4 novel genetic loci associated with TPOAb concentrations and positivity gives further insight into the genetic underpinnings of hypothyroidism. A GRS showed strong and graded associations with markers of thyroid function and disease in independent population-based studies.
ISSN	0021972X
e-ISSN	19457197
DOI	10.1210/jc.2014-4352
Journal	The Journal of Clinical Endocrinology & Metabolism
Issue Number	5
Volume Number	100
Language	English
Publisher	Oxford University Press
Publisher Date	2015-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Genetic Predisposition To Disease Iodide Peroxidase Immunology Thyroid Diseases Genetics Genome-wide Association Study Polymorphism, Single Nucleotide Prospective Studies Risk Factors Blood Thyrotropin Thyroxine Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Endocrinology Discipline Metabolism
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology

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