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GWAS Study

Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder.

Rajagopal VM, Duan J, Vilar-Ribó L et al.

35927488 PubMed ID
GWAS Study Type
53181 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

RV
Rajagopal VM
DJ
Duan J
VL
Vilar-Ribó L
GJ
Grove J
ZT
Zayats T
RJ
Ramos-Quiroga JA
SF
Satterstrom FK
AM
Artigas MS
BJ
Bybjerg-Grauholm J
BM
Bækvad-Hansen M
AT
Als TD
RA
Rosengren A
DM
Daly MJ
NB
Neale BM
NM
Nordentoft M
WT
Werge T
MO
Mors O
HD
Hougaard DM
MP
Mortensen PB
RM
Ribasés M
BA
Børglum AD
DD
Demontis D
Chapter II

Abstract

Summary of the research findings

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes. Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants. Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.

14,878 Danish ancestry cases, 38,303 Danish ancestry controls

Chapter III

Study Statistics

Key metrics and study information

53181
Total Participants
GWAS
Study Type
No
Replicated
European
Ancestry
Denmark
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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