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

TitleA genetic risk score for thyroid peroxidase antibodies associates with clinical thyroid disease in community-based populations.
Publication TypeJournal Article
Year of Publication2015
AuthorsSchultheiss UT, Teumer A, Medici M, Li Y, Daya N, Chaker L, Homuth G, Uitterlinden AG, Nauck M, Hofman A, Selvin E, Völzke H, Peeters RP
Secondary AuthorsKöttgen A
JournalJ Clin Endocrinol Metab
Volume100
Issue5
PaginationE799-807
Date Published2015 May
ISSN1945-7197
KeywordsFemale, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Iodide Peroxidase, Male, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Thyroid Diseases, Thyrotropin, Thyroxine
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

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.

DOI10.1210/jc.2014-4352
Alternate JournalJ Clin Endocrinol Metab
PubMed ID25719932
PubMed Central IDPMC4422885
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
R01DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HSN268201100006C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HSN268201100009C / / PHS HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States