Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism

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dc.contributor.author Ionita-Laza, Iuliana
dc.contributor.author Xu, Bin
dc.contributor.author Makarov, Vlad
dc.contributor.author Buxbaum, Joseph D.
dc.contributor.author Roos, J.L. (Johannes Louw)
dc.contributor.author Gogos, Joseph A.
dc.contributor.author Karayiorgou, Maria
dc.date.accessioned 2015-02-23T06:14:11Z
dc.date.available 2015-02-23T06:14:11Z
dc.date.issued 2014-01
dc.description.abstract We used a family-based cluster detection approach designed to localize significant rare disease–risk variants clusters within a region of interest to systematically search for schizophrenia (SCZ) susceptibility genes within 49 genomic loci previously implicated by de novo copy number variants. Using two independent wholeexome sequencing family datasets and a follow-up autism spectrum disorder (ASD) case/control whole-exome sequencing dataset, we identified variants in one gene, Fanconi-associated nuclease 1 (FAN1), as being associated with both SCZ and ASD. FAN1 is located in a region on chromosome 15q13.3 implicated by a recurrent copy number variant, which predisposes to an array of psychiatric and neurodevelopmental phenotypes. In both SCZ and ASD datasets, rare nonsynonymous risk variants cluster significantly in affected individuals within a 20-kb window that spans several key functional domains of the gene. Our finding suggests that FAN1 is a key driver in the 15q13.3 locus for the associated psychiatric and neurodevelopmental phenotypes. FAN1 encodes a DNA repair enzyme, thus implicating abnormalities in DNA repair in the susceptibility to SCZ or ASD. en_ZA
dc.description.librarian hj2015 en_ZA
dc.description.sponsorship National Science Foundation Grant DMS-1100279 and National Institutes of Health Grants R01MH095797 (to I.I.-L.) and R01MH61399 (to M.K.). en_ZA
dc.description.uri http://www.pnas.org en_ZA
dc.identifier.citation Ionita-Laza, I, Xu, B, Makarov, V, Buxbaum, JD, Roos, JL, Gogos, JA & Karayiorgou, M 2014, Scan statistic-based analysis of exome sequencing data identifies FAN1 At 15q13.3 as a susceptibility gene for schizophrenia and autism', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 1, pp. 343-348. en_ZA
dc.identifier.issn 0027-8424 (print)
dc.identifier.issn 1091-6490 (online)
dc.identifier.other 10.1073/pnas.1309475110
dc.identifier.uri http://hdl.handle.net/2263/43752
dc.language.iso en en_ZA
dc.publisher National Academy of Sciences en_ZA
dc.rights © 2014 by the National Academy of Sciences en_ZA
dc.subject Schizophrenia (SCZ) en_ZA
dc.subject Autism spectrum disorder (ASD) en_ZA
dc.subject Fanconi-associated nuclease 1 (FAN1) en_ZA
dc.subject Whole exome sequencing en_ZA
dc.subject Copy number variation en_ZA
dc.title Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism en_ZA
dc.type Postprint Article en_ZA


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