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Integrating evoluti...
Integrating evolutionary and regulatory information with multispecies approach implicates genes and pathways in obsessive-compulsive disorder
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Noh, Hyun Ji (author)
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Tang, Ruqi (author)
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Flannick, Jason (author)
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show more...
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O'Dushlaine, Colm (author)
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Swofford, Ross (author)
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Howrigan, Daniel (author)
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Genereux, Diane P. (author)
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Johnson, Jeremy (author)
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van Grootheest, Gerard (author)
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Grunblatt, Edna (author)
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Andersson, Erik (author)
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Djurfeldt, Diana R. (author)
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Patel, Paresh D. (author)
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Koltookian, Michele (author)
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Hultman, Christina M. (author)
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Pato, Michele T. (author)
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Pato, Carlos N. (author)
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Rasmussen, Steven A. (author)
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Jenike, Michael A. (author)
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Hanna, Gregory L. (author)
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Stewart, S. Evelyn (author)
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Knowles, James A. (author)
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Ruhrmann, Stephan (author)
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Grabe, Hans-Joergen (author)
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Wagner, Michael (author)
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Ruck, Christian (author)
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Mathews, Carol A. (author)
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Walitza, Susanne (author)
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Cath, Danielle C. (author)
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Feng, Guoping (author)
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Karlsson, Elinor K. (author)
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Lindblad-Toh, Kerstin (author)
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(publisher)
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(publisher)
- NATURE PUBLISHING GROUP 2017
- 2017
- English.
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In: Nature Communications. - 2041-1723. ; 8
Abstract
Subject headings
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- Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 x 10(-11)) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.
Subject headings
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Medical Genetics (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska och farmaceutiska grundvetenskaper (hsv)
- Medicinsk genetik (hsv)
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- By the author/editor
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Noh, Hyun Ji
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Tang, Ruqi
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Flannick, Jason
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O'Dushlaine, Col ...
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Swofford, Ross
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Howrigan, Daniel
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show more...
-
Genereux, Diane ...
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Johnson, Jeremy
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van Grootheest, ...
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Grunblatt, Edna
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Andersson, Erik
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Djurfeldt, Diana ...
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Patel, Paresh D.
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Koltookian, Mich ...
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Hultman, Christi ...
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Pato, Michele T.
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Pato, Carlos N.
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Rasmussen, Steve ...
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Jenike, Michael ...
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Hanna, Gregory L ...
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Stewart, S. Evel ...
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Knowles, James A ...
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Ruhrmann, Stepha ...
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Grabe, Hans-Joer ...
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Wagner, Michael
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Ruck, Christian
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Mathews, Carol A ...
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Walitza, Susanne
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Cath, Danielle C ...
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Feng, Guoping
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Karlsson, Elinor ...
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Lindblad-Toh, Ke ...
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