Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study

被引：3

作者：

Hegemann, Laura ^{[1
,2
,3
]}

Corfield, Elizabeth C. ^{[1
,2
]}

Askelund, Adrian Dahl ^{[1
,2
,3
]}

Allegrini, Andrea G. ^{[4
,5
]}

Askeland, Ragna Bugge ^{[1
]}

Ronald, Angelica ^{[7
]}

Ask, Helga ^{[1
,8
]}

St Pourcain, Beate ^{[9
,10
,11
]}

Andreassen, Ole A. ^{[6
,12
]}

Hannigan, Laurie J. ^{[1
,2
,10
]}

Havdahl, Alexandra ^{[1
,2
,8
]}

机构：

[1] Norwegian Inst Publ Hlth, PsychGen Ctr Genet Epidemiol & Mental Hlth, Oslo, Norway

[2] Lovisenberg Diaconal Hosp, Nic Waals Inst, Oslo, Norway

[3] Univ Oslo, Dept Psychol, Oslo, Norway

[4] UCL, Fac Brain Sci, Dept Clin Educ & Hlth Psychol, Div Psychol & Language Sci, London, England

[5] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci, London, England

[6] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[7] Univ Surrey, Fac Hlth & Med Sci, Sch Psychol, Guildford, England

[8] Univ Oslo, PROMENTA Res Ctr, Dept Psychol, Oslo, Norway

[9] Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands

[10] Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol, England

[11] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands

[12] Univ Oslo, Inst Clin Med, Oslo, Norway

来源：

MOLECULAR AUTISM | 2024年 / 15卷 / 01期

关键词：

AUTISM SPECTRUM DISORDER; DEFICIT HYPERACTIVITY DISORDER; COMMON; RISK; IDENTIFICATION; QUESTIONNAIRE; SCHIZOPHRENIA; SYMPTOMS; PROFILE; ADHD;

D O I：

10.1186/s13229-024-00599-0

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations.Methods In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests.Results We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items r g range = - 0.27-0.78), ADHD (items r g range = - 0.40-1), and schizophrenia (items r g range = - 0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other.Conclusions These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs.

引用

页数：15