Microdeletions of 3q29 confer high risk for schizophrenia

Jennifer Gladys Mulle, Anne F. Dodd, John A. McGrath, Paula S. Wolyniec, Adele A. Mitchell, Amol C. Shetty, Nara Sobreira, David Valle, M. Katharine Rudd, Glen Satten, David J. Cutler, Ann E Pulver, Stephen T. Warren

Research output: Contribution to journalArticle

Abstract

Schizophrenia (SZ) is a severe psychiatric illness that affects ∼1% of the population and has a strong genetic underpinning. Recently, genome-wide analysis of copy-number variation (CNV) has implicated rare and de novo events as important in SZ. Here, we report a genome-wide analysis of 245 SZ cases and 490 controls, all of Ashkenazi Jewish descent. Because many studies have found an excess burden of large, rare deletions in cases, we limited our analysis to deletions over 500 kb in size. We observed seven large, rare deletions in cases, with 57% of these being de novo. We focused on one 836 kb de novo deletion at chromosome 3q29 that falls within a 1.3-1.6 Mb deletion previously identified in children with intellectual disability (ID) and autism, because increasing evidence suggests an overlap of specific rare copy-number variants (CNVs) between autism and SZ. By combining our data with prior CNV studies of SZ and analysis of the data of the Genetic Association Information Network (GAIN), we identified six 3q29 deletions among 7545 schizophrenic subjects and one among 39,748 controls, resulting in a statistically significant association with SZ (p = 0.02) and an odds ratio estimate of 17 (95% confidence interval: 1.36-1198.4). Moreover, this 3q29 deletion region contains two linkage peaks from prior SZ family studies, and the minimal deletion interval implicates 20 annotated genes, including PAK2 and DLG1, both paralogous to X-linked ID genes and now strong candidates for SZ susceptibility.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalAmerican Journal of Human Genetics
Volume87
Issue number2
DOIs
StatePublished - Aug 13 2010

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Schizophrenia
Autistic Disorder
Intellectual Disability
Genome
Chromosome Deletion
Information Services
Disabled Children
Genes
Psychiatry
Odds Ratio
Confidence Intervals
Population

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Mulle, J. G., Dodd, A. F., McGrath, J. A., Wolyniec, P. S., Mitchell, A. A., Shetty, A. C., ... Warren, S. T. (2010). Microdeletions of 3q29 confer high risk for schizophrenia. American Journal of Human Genetics, 87(2), 229-236. https://doi.org/10.1016/j.ajhg.2010.07.013

Microdeletions of 3q29 confer high risk for schizophrenia. / Mulle, Jennifer Gladys; Dodd, Anne F.; McGrath, John A.; Wolyniec, Paula S.; Mitchell, Adele A.; Shetty, Amol C.; Sobreira, Nara; Valle, David; Rudd, M. Katharine; Satten, Glen; Cutler, David J.; Pulver, Ann E; Warren, Stephen T.

In: American Journal of Human Genetics, Vol. 87, No. 2, 13.08.2010, p. 229-236.

Research output: Contribution to journalArticle

Mulle, JG, Dodd, AF, McGrath, JA, Wolyniec, PS, Mitchell, AA, Shetty, AC, Sobreira, N, Valle, D, Rudd, MK, Satten, G, Cutler, DJ, Pulver, AE & Warren, ST 2010, 'Microdeletions of 3q29 confer high risk for schizophrenia', American Journal of Human Genetics, vol. 87, no. 2, pp. 229-236. https://doi.org/10.1016/j.ajhg.2010.07.013
Mulle JG, Dodd AF, McGrath JA, Wolyniec PS, Mitchell AA, Shetty AC et al. Microdeletions of 3q29 confer high risk for schizophrenia. American Journal of Human Genetics. 2010 Aug 13;87(2):229-236. https://doi.org/10.1016/j.ajhg.2010.07.013
Mulle, Jennifer Gladys ; Dodd, Anne F. ; McGrath, John A. ; Wolyniec, Paula S. ; Mitchell, Adele A. ; Shetty, Amol C. ; Sobreira, Nara ; Valle, David ; Rudd, M. Katharine ; Satten, Glen ; Cutler, David J. ; Pulver, Ann E ; Warren, Stephen T. / Microdeletions of 3q29 confer high risk for schizophrenia. In: American Journal of Human Genetics. 2010 ; Vol. 87, No. 2. pp. 229-236.
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