Manuel Mattheisen

Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • W. Guo, NIMH, National Institutes of Health (NIH) - USA, NIH National Institute of Mental Health (NIMH), Unit Stat Genom, Intramural Res Programs, NIH
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  • J. F. Samuels, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • Y. Wang, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • H. Cao, Elsevier Inc, Elsevier, Reed Elsevier
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  • M. Ritter, NIMH, National Institutes of Health (NIH) - USA, NIH National Institute of Mental Health (NIMH), Unit Stat Genom, Intramural Res Programs, NIH
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  • P. S. Nestadt, Johns Hopkins Univ, Johns Hopkins University, Bloomberg Sch Publ Hlth, Dept Mental Hlth
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  • J. Krasnow, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • B. D. Greenberg, Brown Med Sch, Brown University, Dept Psychiat & Human Behav
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  • A. J. Fyer, Columbia Univ, Columbia University, New York State Psychiatry Institute, Coll Phys & Surg, New York State Psychiat Inst
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  • J. T. McCracken, Univ Calif Los Angeles, University of California System, University of California Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci
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  • D. A. Geller, Harvard Med Sch, Harvard University, Dept Hlth Care Policy
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  • D. L. Murphy, NIMH, National Institutes of Health (NIH) - USA, NIH National Institute of Mental Health (NIMH), Clin Sci Lab
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  • J. A. Knowles, Univ Southern Calif, University of Southern California, Dept Psychiat & Behav Sci, Keck Sch Med
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  • M. A. Grados, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • M. A. Riddle, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • S. A. Rasmussen, Brown Med Sch, Brown University, Dept Psychiat & Human Behav
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  • N. C. McLaughlin, Brown Med Sch, Brown University, Dept Psychiat & Human Behav
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  • E. L. Nurmi, Univ Calif Los Angeles, University of California System, University of California Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci
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  • K. D. Askland, Brown Med Sch, Brown University, Dept Psychiat & Human Behav
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  • B. A. Culten, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • J. Piacentini, Univ Calif Los Angeles, University of California System, University of California Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci
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  • D. L. Pauls, Massachusetts Gen Hosp, Harvard University, VA Boston Healthcare System, Massachusetts General Hospital, Dept Psychiat
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  • O. J. Bienvenu, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • S. E. Stewart, Univ British Columbia, University of British Columbia, Dept Psychiat
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  • F. S. Goes, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • B. Maher, Johns Hopkins Univ, Johns Hopkins University, Bloomberg Sch Publ Hlth, Dept Mental Hlth
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  • A. E. Pulver, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • D. Valle, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Inst Human Genet
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  • M. Mattheisen
  • J. Qian, Fudan Univ, Fudan University, Inst Life Sci
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  • G. Nestad, Johns Hopkins Univ, Johns Hopkins University, Sch Med, Dept Psychiat & Behav Sci
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  • Y. Y. Shugart, NIMH, National Institutes of Health (NIH) - USA, NIH National Institute of Mental Health (NIMH), Unit Stat Genom, Intramural Res Programs, NIH

Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9 x 10(-7) in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data. Published by Elsevier B.V.

Original languageEnglish
JournalEuropean Neuropsychopharmacology
Volume27
Issue7
Pages (from-to)657-666
Number of pages10
ISSN0924-977X
DOIs
Publication statusPublished - Jul 2017

    Research areas

  • OCD, ASD, GWAS, Meta-analysis, Polygenic score, Heritability, OBSESSIVE-COMPULSIVE DISORDER, AUTISM SPECTRUM DISORDERS, CHILDREN, ADULTS, ASSOCIATION, ANXIETY, TRAITS, METAANALYSIS, ADOLESCENTS, POPULATION

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