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

dc.contributor.authorIonita-Laza, Iuliana
dc.contributor.authorXu, Bin
dc.contributor.authorMakarov, Vlad
dc.contributor.authorBuxbaum, Joseph D.
dc.contributor.authorRoos, J.L. (Johannes Louw)
dc.contributor.authorGogos, Joseph A.
dc.contributor.authorKarayiorgou, Maria
dc.date.accessioned2015-02-23T06:14:11Z
dc.date.available2015-02-23T06:14:11Z
dc.date.issued2014-01
dc.description.abstractWe 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.librarianhj2015en_ZA
dc.description.sponsorshipNational 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.urihttp://www.pnas.orgen_ZA
dc.identifier.citationIonita-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.issn0027-8424 (print)
dc.identifier.issn1091-6490 (online)
dc.identifier.other10.1073/pnas.1309475110
dc.identifier.urihttp://hdl.handle.net/2263/43752
dc.language.isoenen_ZA
dc.publisherNational Academy of Sciencesen_ZA
dc.rights© 2014 by the National Academy of Sciencesen_ZA
dc.subjectSchizophrenia (SCZ)en_ZA
dc.subjectAutism spectrum disorder (ASD)en_ZA
dc.subjectFanconi-associated nuclease 1 (FAN1)en_ZA
dc.subjectWhole exome sequencingen_ZA
dc.subjectCopy number variationen_ZA
dc.titleScan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autismen_ZA
dc.typePostprint Articleen_ZA

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