Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families

Sonja Marie Henriksen Labianca; Jette Labianca; Anne Katrine Pagsberg; Klaus Damgaard Jakobsen; Vivek  Appadurai; Alfonso Buil; Thomas Mears Werge

doi:10.1007/s10803-020-04552-x

Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families

Sonja Marie Henriksen Labianca, Jette Labianca, Anne Katrine Pagsberg, Klaus Damgaard Jakobsen, Vivek Appadurai, Alfonso Buil, Thomas Mears Werge

10 Citations (Scopus)

Abstract

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10% in comorbid ASD/ADHD, 4% in ASD and 2% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two.

Original language	English
Journal	Journal of Autism and Developmental Disorders
Volume	51
Issue number	1
Pages (from-to)	276-285
Number of pages	10
ISSN	0162-3257
DOIs	https://doi.org/10.1007/s10803-020-04552-x
Publication status	Published - Jan 2021

Keywords

Adolescent
Adult
Attention Deficit Disorder with Hyperactivity/diagnosis
Autistic Disorder/diagnosis
Child
Comorbidity
DNA Copy Number Variations/genetics
Denmark/epidemiology
Female
Humans
Male
Multifactorial Inheritance/genetics
Predictive Value of Tests
Risk Factors
Polygenic risk score
Families
Autism spectrum disorder
Attention deficit/hyperactivity disorder
Copy number variants

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10.1007/s10803-020-04552-x

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title = "Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families",

abstract = "Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10\% in comorbid ASD/ADHD, 4\% in ASD and 2\% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two.",

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author = "Labianca, \{Sonja Marie Henriksen\} and Jette Labianca and Pagsberg, \{Anne Katrine\} and Jakobsen, \{Klaus Damgaard\} and Vivek Appadurai and Alfonso Buil and Werge, \{Thomas Mears\}",

year = "2021",

month = jan,

doi = "10.1007/s10803-020-04552-x",

language = "English",

volume = "51",

pages = "276--285",

journal = "Journal of Autism and Developmental Disorders",

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T1 - Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families

AU - Labianca, Sonja Marie Henriksen

AU - Labianca, Jette

AU - Pagsberg, Anne Katrine

AU - Jakobsen, Klaus Damgaard

AU - Appadurai, Vivek

AU - Buil, Alfonso

AU - Werge, Thomas Mears

PY - 2021/1

Y1 - 2021/1

N2 - Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10% in comorbid ASD/ADHD, 4% in ASD and 2% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two.

AB - Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10% in comorbid ASD/ADHD, 4% in ASD and 2% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two.

KW - Adolescent

KW - Adult

KW - Attention Deficit Disorder with Hyperactivity/diagnosis

KW - Autistic Disorder/diagnosis

KW - Child

KW - Comorbidity

KW - DNA Copy Number Variations/genetics

KW - Denmark/epidemiology

KW - Female

KW - Humans

KW - Male

KW - Multifactorial Inheritance/genetics

KW - Predictive Value of Tests

KW - Risk Factors

KW - Polygenic risk score

KW - Families

KW - Autism spectrum disorder

KW - Attention deficit/hyperactivity disorder

KW - Copy number variants

UR - https://www.scopus.com/pages/publications/85085512876

U2 - 10.1007/s10803-020-04552-x

DO - 10.1007/s10803-020-04552-x

M3 - Journal article

C2 - 32462456

SN - 0162-3257

VL - 51

SP - 276

EP - 285

JO - Journal of Autism and Developmental Disorders

JF - Journal of Autism and Developmental Disorders

IS - 1

ER -

Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families

Abstract

Keywords

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