Format

Send to

Choose Destination
See comment in PubMed Commons below
Nature. 2014 Jan 16;505(7483):361-6. doi: 10.1038/nature12818. Epub 2013 Dec 18.

CNVs conferring risk of autism or schizophrenia affect cognition in controls.

Author information

1
1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland [2].
2
1] Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany [2].
3
deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland.
4
Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland.
5
Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany.
6
1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland [2] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland.
7
Institute of Psychiatry, King's College, 16 De Crespigny Park, London SE5 8AF, UK.
8
1] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavík, Iceland [2] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland.
9
Röntgen Domus, Egilsgötu 3, IS-101 Reykjavík, Iceland.
10
Mental Health Centre Sct. Hans, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Boserupvej 2, DK-4000 Roskilde, Denmark.
11
Tailored Therapeutics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center DC 1940, Indianapolis, Indiana 46285, USA.
12
H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
13
University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland.
14
The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland.
15
1] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland [2] The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland.

Abstract

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.

PMID:
24352232
DOI:
10.1038/nature12818
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center