• norsk
    • English
  • English 
    • norsk
    • English
  • Login
View Item 
  •   Home
  • Faculty of Medicine
  • Department of Biomedicine
  • Department of Biomedicine
  • View Item
  •   Home
  • Faculty of Medicine
  • Department of Biomedicine
  • Department of Biomedicine
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Novel loci associated with attention-deficit/hyperactivity disorder are revealed by leveraging polygenic overlap with educational attainment

Shadrin, Alexey A.; Smeland, Olav Bjerkehagen; Zayats, Tetyana; Schork, Andrew J; Frei, Oleksandr; Bettella, Francesco; Witoelar, Aree; Li, Wen; Eriksen, Jon Alm; Krull, Florian; Djurovic, Srdjan; Faraone, Stephen V.; Reichborn-Kjennerud, Ted; Thompson, Wesley K; Johansson, Stefan; Haavik, Jan; Dale, Anders; Wang, Yunpeng; Andreassen, Ole Andreas
Peer reviewed, Journal article
Accepted version
Thumbnail
View/Open
Accepted version (4.379Mb)
URI
https://hdl.handle.net/1956/20183
Date
2018-02
Metadata
Show full item record
Collections
  • Department of Biomedicine [439]
Original version
Shadrin AA, Smeland OB, Zayats T, Schork AJ, Frei O, Bettella F, Witoelar AW, Li W, Eriksen JA, Krull F, Djurovic S, Faraone SV, Reichborn-Kjennerud T, Thompson WK, Johansson S, Haavik J, Dale A, Wang Y, Andreassen OA. Novel loci associated with attention-deficit/hyperactivity disorder are revealed by leveraging polygenic overlap with educational attainment. Journal of the American Academy of Child and Adolescent Psychiatry. 2018;57(2):86-95   https://doi.org/10.1016/j.jaac.2017.11.013
Abstract
Objective Attention-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. Method A 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. Results At 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 (rg=−0.403, p=7.90×10−8) and >10-fold mutual enrichment of SNPs associated with both traits. Conclusion We 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.
Publisher
Elsevier
Journal
Journal of the American Academy of Child and Adolescent Psychiatry
Copyright
Copyright 2017 American Academy of Child and Adolescent Psychiatry

Contact Us | Send Feedback

Privacy policy
DSpace software copyright © 2002-2019  DuraSpace

Service from  Unit
 

 

Browse

ArchiveCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDocument TypesJournalsThis CollectionBy Issue DateAuthorsTitlesSubjectsDocument TypesJournals

My Account

Login

Statistics

View Usage Statistics

Contact Us | Send Feedback

Privacy policy
DSpace software copyright © 2002-2019  DuraSpace

Service from  Unit