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A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.
Tuesday,2013-04-30 15:30 America/Los_Angeles — chsadmin
| Title | A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Porcu, E, Medici, M, Pistis, G, Volpato, CB, Wilson, SG, Cappola, AR, Bos, SD, Deelen, J, Heijer, Mden, Freathy, RM, Lahti, J, Liu, C, Lopez, LM, Nolte, IM, O'Connell, JR, Tanaka, T, Trompet, S, Arnold, A, Bandinelli, S, Beekman, M, Böhringer, S, Brown, SJ, Buckley, BM, Camaschella, C, de Craen, AJM, Davies, G, de Visser, MCH, Ford, I, Forsen, T, Frayling, TM, Fugazzola, L, Gögele, M, Hattersley, AT, Hermus, AR, Hofman, A, Houwing-Duistermaat, JJ, Jensen, RA, Kajantie, E, Kloppenburg, M, Lim, EM, Masciullo, C, Mariotti, S, Minelli, C, Mitchell, BD, Nagaraja, R, Netea-Maier, RT, Palotie, A, Persani, L, Piras, MG, Psaty, BM, Räikkönen, K, J Richards, B, Rivadeneira, F, Sala, C, Sabra, MM, Sattar, N, Shields, BM, Soranzo, N, Starr, JM, Stott, DJ, Sweep, FCGJ, Usala, G, van der Klauw, MM, van Heemst, D, van Mullem, A, Vermeulen, SH, W Visser, E, Walsh, JP, Westendorp, RGJ, Widen, E, Zhai, G, Cucca, F, Deary, IJ, Eriksson, JG, Ferrucci, L, Fox, CS, J Jukema, W, Kiemeney, LA, Pramstaller, PP, Schlessinger, D, Shuldiner, AR, Slagboom, EP, Uitterlinden, AG, Vaidya, B, Visser, TJ, Wolffenbuttel, BHR, Meulenbelt, I, Rotter, JI, Spector, TD, Hicks, AA, Toniolo, D, Sanna, S, Peeters, RP, Naitza, S |
| Journal | PLoS Genet |
| Volume | 9 |
| Issue | 2 |
| Pagination | e1003266 |
| Date Published | 2013 |
| ISSN | 1553-7404 |
| Keywords | Female, Genome-Wide Association Study, Humans, Hyperthyroidism, Hypothyroidism, Male, Phenotype, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Sex Characteristics, Signal Transduction, Thyroid Gland, Thyrotropin, Thyroxine |
| Abstract | <p>Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.</p> |
| DOI | 10.1371/journal.pgen.1003266 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 23408906 |
| PubMed Central ID | PMC3567175 |
| Grant List | ETM/55 / / Chief Scientist Office / United Kingdom WT091310,085541/Z/08/Z / / Wellcome Trust / United Kingdom N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States U01 HL72515 / HL / NHLBI NIH HHS / United States N01-AG-1-2109 / AG / NIA NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States 263 MD 821336 / MD / NIMHD NIH HHS / United States AG-15928 / AG / NIA NIH HHS / United States / / Medical Research Council / United Kingdom / / Biotechnology and Biological Sciences Research Council / United Kingdom R01 AG18728 / AG / NIA NIH HHS / United States / / Department of Health / United Kingdom AG-20098 / AG / NIA NIH HHS / United States M01 RR 16500 / RR / NCRR NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States WT098051 / / Wellcome Trust / United Kingdom MR/K026992/1 / / Medical Research Council / United Kingdom WT089062 / / Wellcome Trust / United Kingdom N01-HC-85086 / HC / NHLBI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States / / Intramural NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States / / Canadian Institutes of Health Research / Canada M01 RR 000052 / RR / NCRR NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States G0700704 / / Medical Research Council / United Kingdom N01-HC-85079 / HC / NHLBI NIH HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom N01-HC-85239 / HC / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States 263 MD 9164 / MD / NIMHD NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States |