Microduplications of 16p11.2 are Associated with Schizophrenia

doi:10.1038/NG.474

Open AccessJournal ArticleDOI

Microduplications of 16p11.2 are Associated with Schizophrenia

Shane McCarthy, +77 more

- 01 Nov 2009 -

Nature Genetics

- Vol. 41, Iss: 11, pp 1223-1227

TLDR

A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder, and autism, while the reciprocal microdeletion was associated only with autism and developmental disorders.

Abstract:

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1, 2, 3. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 10-5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 10-7), bipolar disorder (P = 0.017) and autism (P = 1.9 10-7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 10-13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).

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References

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Strong Association of De Novo Copy Number Mutations with Autism

Jonathan Sebat, +31 more

- 20 Apr 2007 -

Science

TL;DR: Findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.

...read moreread less

Journal ArticleDOI

Large recurrent microdeletions associated with schizophrenia

Hreinn Stefansson, +81 more

- 11 Sep 2008 -

Nature

TL;DR: In a genome-wide search for CNVs associating with schizophrenia, a population-based sample was used to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring and three deletions significantly associate with schizophrenia and related psychoses in the combined sample.

...read moreread less

Journal ArticleDOI

Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia

Tom Walsh, +37 more

- 25 Apr 2008 -

Science

TL;DR: The results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia, and disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways.

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Structural variation of chromosomes in autism spectrum disorder.

Christian R. Marshall, +34 more

- 08 Feb 2008 -

American Journal of Human Genetics

TL;DR: The results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility.

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