Genome-wide Association Study Identifies Four Genetic Loci Associated with Thyroid Volume and Goiter Risk

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• 作者：Alexander Teumer¹ ; ¹⁰ ; Rajesh Rawal² ; ¹⁰ ; Georg Homuth¹ ; ¹⁰ ; Florian Ernst¹ ; Margit Heier⁹ ; Matthias Evert³ ; Frank Dombrowski³ ; Uwe Vö ; lker¹ ; Matthias Nauck⁴ ; Dö ; rte Radke⁵ ; Till Ittermann⁵ ; Reiner Biffar⁶ ; Angela Dö ; ring² ; Christian Gieger² ; Norman Klopp² ; H.-Erich Wichmann² ; ⁷ ; ⁸ ; Henri Wallaschofski⁴ ; Christa Meisinger⁹ ; ¹⁰ ; Henry Vö ; lzke⁵ ; ¹⁰ ; ^{voelzke@uni-greifswald.de"" rel=""nofollow}
• 刊名：The American Journal of Human Genetics
• 出版年：2011
• 出版时间：13 May 2011
• 年：2011
• 卷：88
• 期：5
• 页码：664-673
• 全文大小：902 K

文摘

Thyroid disorders such as goiters represent important diseases, especially in iodine-deficient areas. Sibling studies have demonstrated that genetic factors substantially contribute to the interindividual variation of thyroid volume. We performed a genome-wide association study of this phenotype by analyzing a discovery cohort consisting of 3620 participants of the Study of Health in Pomerania (SHIP). Four genetic loci were associated with thyroid volume on a genome-wide level of significance. Of these, two independent loci are located upstream of and within CAPZB, which encodes the β subunit of the barbed-end F-actin binding protein that modulates actin polymerization, a process crucial in the colloid engulfment during thyroglobulin mobilization in the thyroid. The third locus marks FGF7, which encodes fibroblast growth factor 7. Members of this protein family have been discussed as putative signal molecules involved in the regulation of thyroid development. The fourth locus represents a “gene desert” on chromosome 16q23, located directly downstream of the predicted coding sequence LOC440389, which, however, had already been removed from the NCBI database as a result of the standard genome annotation processing at the time that this study was initiated. Experimental proof of the formerly predicted mature mRNA, however, demonstrates that LOC440389 indeed represents a real gene. All four associations were replicated in an independent sample of 1290 participants of the KORA study. These results increase the knowledge about genetic factors and physiological mechanisms influencing thyroid volume.