Genome-wide association studies of infant and toddler temperament in European and multi-ancestry populations.
Hollowell A., Gui A., Wigdor E., Morgan MJ., Hannigan LJ., Corfield EC., Pool R., Bruins S., Ask H., Middeldorp CM., Pourcain BS., Bartels M., Boomsma DI., Hartman CA., Noda A., Takahashi I., Ishikuro M., Obara T., Kuriyama S., Mufford MS., Lake MT., Stein DJ., Zar HJ., Hoffman N., Robinson EB., Børglum AD., Zhang X., Warrier V., Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium ., Arichi T., Johnson MH., Dudbridge F., Sanders SJ., Havdahl A., Ronald A.
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.