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<p>Autoimmune hypothyroidism (Hashimoto’s thyroiditis) is common and has a strong genetic component. Here we performed multi-ancestry genome-wide association meta-analyses encompassing 48,694 Hashimoto’s thyroiditis cases, using a precise case definition, and 1,044,134 controls. We identified 155 significant (<i>P</i> &lt; 5 × 10<sup>−8</sup>) independent genetic associations, of which 45 variants and 19 loci were not previously associated with hypothyroidism. Six loci were specific for individuals of European ancestry reference populations. Functional enrichment analyses of Hashimoto’s thyroiditis-associated genes highlighted immune cells and the spleen, underpinning the importance of T cells in Hashimoto’s thyroiditis development. This observation was further supported by 161 significant colocalizations with expression quantitative trait loci in immune cells and 40 in thyroid tissue (for example, <i>TG, VAV3</i>, <i>IRF5</i>), highlighting the interplay between the immune system and the thyroid. Mendelian randomization indicated causal effects of Hashimoto’s thyroiditis on cardiovascular traits and expected associations with thyroid hormone levels.</p>

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Multi-ancestry genome-wide association analyses provide insights into the genetic basis of Hashimoto’s thyroiditis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Melissa N. Bujnis,
  • Rosalie B. T. M. Sterenborg,
  • Yong Li,
  • Bjørn Olav Åsvold,
  • Luka Brčić,
  • Vesna Boraska Perica,
  • Anav Babbar,
  • Joshua C. Denny,
  • Lars G. Fritsche,
  • Masahiro Kanai,
  • Ilze Konrade,
  • Graham Leese,
  • Eirini Marouli,
  • Andres Metspalu,
  • Marta R. Moksnes,
  • Bhramar Mukherjee,
  • Yukinori Okada,
  • Colin N. A. Palmer,
  • Areti Papadopoulou,
  • Raitis Peculis,
  • Vita Rovite,
  • Peter J. Sauer,
  • Enrique Soto-Pedre,
  • Sundararajan Srinivasan,
  • Inga Steinbrenner,
  • Maris Teder-Laving,
  • Bin Wang,
  • Antoine Weihs,
  • Chenjie Zeng,
  • Jin Zhou,
  • XiCheng Song,
  • Lynn B. Jorde,
  • Marco Medici,
  • Alexander Teumer

摘要

Autoimmune hypothyroidism (Hashimoto’s thyroiditis) is common and has a strong genetic component. Here we performed multi-ancestry genome-wide association meta-analyses encompassing 48,694 Hashimoto’s thyroiditis cases, using a precise case definition, and 1,044,134 controls. We identified 155 significant (P < 5 × 10−8) independent genetic associations, of which 45 variants and 19 loci were not previously associated with hypothyroidism. Six loci were specific for individuals of European ancestry reference populations. Functional enrichment analyses of Hashimoto’s thyroiditis-associated genes highlighted immune cells and the spleen, underpinning the importance of T cells in Hashimoto’s thyroiditis development. This observation was further supported by 161 significant colocalizations with expression quantitative trait loci in immune cells and 40 in thyroid tissue (for example, TG, VAV3, IRF5), highlighting the interplay between the immune system and the thyroid. Mendelian randomization indicated causal effects of Hashimoto’s thyroiditis on cardiovascular traits and expected associations with thyroid hormone levels.