Polygenic Risk Scores for Developmental Disorders, Neuromotor Functioning During Infancy, and Autistic Traits in Childhood

被引:29
作者
Serdarevic, Fadila [1 ,2 ,4 ]
Tiemeier, Henning [2 ,7 ]
Jansen, Philip R. [1 ,2 ,3 ]
Alemany, Silvia [9 ]
Xerxa, Yllza [1 ,2 ]
Neumann, Alexander [2 ]
Robinson, Elise [8 ]
Hillegers, Manon H. J. [1 ]
Verhulst, Frank C. [2 ]
Ghassabian, Akhgar [4 ,5 ,6 ]
机构
[1] Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands
[2] Sophia Childrens Hosp Rotterdam, Dept Child & Adolescent Psychiat, Erasmus Med Ctr, Rotterdam, Netherlands
[3] Vrije Univ Amsterdam, Ctr Neurosci & Cognit Res, Dept Complex Trait Genet, Amsterdam Neurosci, Amsterdam, Netherlands
[4] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA
[5] NYU, Dept Populat Hlth, Sch Med, New York, NY USA
[6] NYU, Dept Environm Med, Sch Med, 550 1St Ave, New York, NY 10016 USA
[7] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,Kresge Bldg,Room 619, Boston, MA 02115 USA
[8] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
[9] Univ Pompeu Fabra, Barcelona Inst Global Hlth, CIBER Epidemiol & Salud Publ, Barcelona, Spain
关键词
ADHD; Autism; Cohort; Infant; Neuromotor; Polygenic risk score; Population based; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SPECTRUM DISORDER; GENETIC RISK; GENERAL-POPULATION; ASSOCIATION; ABNORMALITIES; CHILDREN; EMERGENCE; BRAIN;
D O I
10.1016/j.biopsych.2019.06.006
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
BACKGROUND: Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. METHODS: In a population-based cohort in The Netherlands (2002-2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9-20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. RESULTS: Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism-based heritability of overall motor development was 20% (SE = .21) and of autistic traits was 68% (SE = .26). The genetic correlation between overall motor development and autistic traits was .35 (SE = .21, p < .001). CONCLUSIONS: We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood.
引用
收藏
页码:132 / 138
页数:7
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