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<p>Early temperament, such as socio-emotional development and activity level, varies widely, yet its underlying biological associations are not understood. We identified genetic variation associated with infant and toddler temperament using genome-wide association meta-analyses. We studied parent-rated emotionality, activity, shyness and sociability (<i>n</i> = 43,963–72,663) in the second and third postnatal years and a cross-age average. Cross-age single nucleotide polymorphism heritabilities for emotionality, activity, shyness and sociability were 6.79% (95% confidence interval (CI), (4.71%, 8.87%)), 9.55% (95% CI, (7.04%, 12.06%)), 15.26% (95% CI, (12.24%, 18.28%)) and 3.42% (95% CI, (1.30%, 5.54%)), respectively. Ten genome-wide significant loci were discovered. Two loci colocalized with expression quantitative trait loci in the adult cortex: <i>RHEBL1</i> (posterior probability, 0.93; associated with activity) and <i>MR1</i> (posterior probability, 0.99; with emotionality). Genetic correlations were observed between early temperament and later outcomes, such as emotionality and adult neuroticism, activity and attention deficit/hyperactivity disorder (ADHD), sociability and autism, and shyness and adult extraversion. Multi-ancestry (<i>n</i> = 56,083–78,894) and European-ancestry analyses gave similar results. Infant and toddler temperament is associated with genetic variation and shows genetic continuity with later outcomes.</p>

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Genome-wide association studies of infant and toddler temperament in European and multi-ancestry populations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Anja Hollowell,
  • Anna Gui,
  • Emilie Wigdor,
  • Morgan J. Morgan,
  • Laurie J. Hannigan,
  • Elizabeth C. Corfield,
  • René Pool,
  • Susanne Bruins,
  • Helga Ask,
  • Christel M. Middeldorp,
  • Beate St Pourcain,
  • Meike Bartels,
  • Dorret I. Boomsma,
  • Catharina A. Hartman,
  • Aoi Noda,
  • Ippei Takahashi,
  • Mami Ishikuro,
  • Taku Obara,
  • Shinichi Kuriyama,
  • Mary S. Mufford,
  • Marilyn T. Lake,
  • Dan J. Stein,
  • Heather J. Zar,
  • Nadia Hoffman,
  • Elise B. Robinson,
  • Anders D. Børglum,
  • Xinhe Zhang,
  • Varun Warrier,
  • Jakob Grove,
  • Isabel Dziobek,
  • Lauren Weiss,
  • Melanie M. de Wit,
  • Mohammed Uddin,
  • Ole A. Andreassen,
  • Richard J. L. Anney,
  • Stephen W. Scherer,
  • Susan S. Kuo,
  • Wonuola A. Akingbuwa,
  • Tomoki Arichi,
  • Mark H. Johnson,
  • Frank Dudbridge,
  • Stephan J. Sanders,
  • Alexandra Havdahl,
  • Angelica Ronald

摘要

Early temperament, such as socio-emotional development and activity level, varies widely, yet its underlying biological associations are not understood. We identified genetic variation associated with infant and toddler temperament using genome-wide association meta-analyses. We studied parent-rated emotionality, activity, shyness and sociability (n = 43,963–72,663) in the second and third postnatal years and a cross-age average. Cross-age single nucleotide polymorphism heritabilities for emotionality, activity, shyness and sociability were 6.79% (95% confidence interval (CI), (4.71%, 8.87%)), 9.55% (95% CI, (7.04%, 12.06%)), 15.26% (95% CI, (12.24%, 18.28%)) and 3.42% (95% CI, (1.30%, 5.54%)), respectively. Ten genome-wide significant loci were discovered. Two loci colocalized with expression quantitative trait loci in the adult cortex: RHEBL1 (posterior probability, 0.93; associated with activity) and MR1 (posterior probability, 0.99; with emotionality). Genetic correlations were observed between early temperament and later outcomes, such as emotionality and adult neuroticism, activity and attention deficit/hyperactivity disorder (ADHD), sociability and autism, and shyness and adult extraversion. Multi-ancestry (n = 56,083–78,894) and European-ancestry analyses gave similar results. Infant and toddler temperament is associated with genetic variation and shows genetic continuity with later outcomes.