Genome-wide association studies of infant and toddler temperament in European and multi-ancestry populations.
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Hollowell Anja, Gui Anna, Wigdor Emilie, Morgan Morgan J, Hannigan Laurie J, Corfield Elizabeth C, Pool René, Bruins Susanne, Ask Helga, Middeldorp Christel M, Pourcain Beate St, Bartels Meike, Boomsma Dorret I, Hartman Catharina A, Noda Aoi, Takahashi Ippei, Ishikuro Mami, Obara Taku, Kuriyama Shinichi, Mufford Mary S, Lake Marilyn T, Stein Dan J, Zar Heather J, Hoffman Nadia, Robinson Elise B, Børglum Anders D, Zhang Xinhe, Warrier Varun, Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium, Arichi Tomoki, Johnson Mark H, Dudbridge Frank, Sanders Stephan J, Havdahl Alexandra, Ronald Angelica
Аннотация
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.