Evidence map›Paper›PMID 29413154›Full record

ArticleJournal of the American Academy of Child and Adolescent Psychiatry2018

Novel Loci Associated With Attention-Deficit/Hyperactivity Disorder Are Revealed by Leveraging Polygenic Overlap With Educational Attainment.

Alexey A Shadrin, Olav B Smeland, Tetyana Zayats, Andrew J Schork, Oleksandr Frei, Francesco Bettella, Aree Witoelar, Wen Li, Jon A Eriksen, Florian Krull and 9 more

Abstract read
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In one paragraph

Article in Journal of the American Academy of Child and Adolescent Psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Alexey A ShadrinNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. Electronic address: a.a.shadrin@medisin.uio.no.
Olav B SmelandNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Tetyana ZayatsK.G. Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway.
Andrew J SchorkUniversity of California, San Diego and Institute of Biological Psychiatry, Medical Health Center, Sct. Hans Hospital and University of Copenhagen, Copenhagen, Denmark.
Oleksandr FreiNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Francesco BettellaNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Aree WitoelarNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Wen LiNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Jon A EriksenNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Florian KrullNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Srdjan DjurovicOslo University Hospital, Oslo, and NORMENT, KG Jebsen Centre for Psychosis Research, University of Bergen.
Stephen V FaraoneKG Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, SUNY Upstate Medical University, Syracuse, New York.
Ted Reichborn-KjennerudDivision of Mental Health, Norwegian Institute of Public Health, Oslo, and Institute of Clinical Medicine, University of Oslo.
Wesley K ThompsonUniversity of California, San Diego.
Stefan JohanssonK.G. Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Jan HaavikK.G. Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital.
Anders M DaleNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and University of California, San Diego.
Yunpeng WangNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; University of California, San Diego, La Jolla, CA.
Ole A AndreassenNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Funding

3/7 Psychiatric Genomics Consortium: Finding actionable variationU01MH109536 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHARNEY, ALEXANDER W, HUCKINS, LAURA MARIANNE · 2016 to 2020
$2.7M
Polygenicity, Pleiotrophy and Power: Novel Statistical Methods for Gene DiscoveryR01GM104400 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI THOMPSON, WESLEY KURT · 2014 to 2017
$1.6M
NIGMS NIH HHS R01 GM104400NIMH NIH HHS U01 MH109536
6 · The paper itself

Abstract

objectiveAttention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable psychiatric condition. By exploiting the reported relationship between ADHD and educational attainment (EA), we aimed to improve discovery of ADHD-associated genetic variants and to investigate genetic overlap between these phenotypes.

methodA conditional/conjunctional false discovery rate (condFDR/conjFDR) method was applied to genome-wide association study (GWAS) data on ADHD (2,064 trios, 896 cases, and 2,455 controls) and EA (n=328,917) to identify ADHD-associated loci and loci overlapping between ADHD and EA. Identified single nucleotide polymorphisms (SNPs) were tested for association in an independent population-based study of ADHD symptoms (n=17,666). Genetic correlation between ADHD and EA was estimated using LD score regression and Pearson correlation.

resultsAt levels of condFDR<0.01 and conjFDR<0.05, we identified 5 ADHD-associated loci, 3 of these being shared between ADHD and EA. None of these loci had been identified in the primary ADHD GWAS, demonstrating the increased power provided by the condFDR/conjFDR analysis. Leading SNPs for 4 of 5 identified regions are in introns of protein coding genes (KDM4A, MEF2C, PINK1, RUNX1T1), whereas the remaining one is an intergenic SNP on chromosome 2 at 2p24. Consistent direction of effects in the independent study of ADHD symptoms was shown for 4 of 5 identified loci. A polygenic overlap between ADHD and EA was supported by significant genetic correlation (r

conclusionWe identified 5 novel loci associated with ADHD and provided evidence for a shared genetic basis between ADHD and EA. These findings could aid understanding of the genetic risk architecture of ADHD and its relation to EA.

Indexed as

Genetic Predisposition to DiseaseAttention Deficit Disorder with HyperactivityChildEducational StatusFemaleGenome-Wide Association StudyHumansJumonji Domain-Containing Histone DemethylasesMaleMultifactorial InheritancePhenotypePolymorphism, Single NucleotideJumonji Domain-Containing Histone DemethylasesKDM4A protein, humanattention-deficit/hyperactivity disorderconditional/conjunctional false discovery rateeducational attainmentgenetic overlap

Identifiers

PMID29413154
PMCPMC5806128

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.