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A common missense variant in the neuregulin 1 gene is associated with both schizophrenia and sudden cardiac death.

Abstract：

BACKGROUND:Both schizophrenia and epilepsy have been linked to increased risk of sudden cardiac death (SCD). We hypothesized that DNA variants within genes previously associated with schizophrenia and epilepsy may contribute to an increased risk of SCD. OBJECTIVE:To investigate the contribution to SCD susceptibility of DNA variants previously implicated in schizophrenia and epilepsy. METHODS:From the ongoing Oregon Sudden Unexpected Death Study, comparisons were performed among 340 SCD cases presenting with ventricular fibrillation and 342 controls. We tested for the association between 17 single-nucleotide polymorphisms (SNPs) mapped to 14 loci previously implicated in schizophrenia and epilepsy by using logistic regression and assuming additive, dominant, and recessive genetic models. RESULTS:The minor allele of the nonsynonymous SNP rs10503929 within the neuregulin 1 gene was associated with SCD under all 3 investigated models, with the strongest association for the recessive genetic model (recessive P = 4.01 × 10(-5), odds ratio [OR] 4.04; additive P = 2.84 × 10(-7), OR 1.9; and dominant P = 9.01 × 10(-6), OR 2.06). To validate our findings, we further explored the association of this variant in the Harvard Cohort SCD study. The SNP rs10503929 was associated with an increased risk of SCD under the recessive genetic model (P = .0005, OR 2.7). This missense variation causes a methionine to threonine change and functional effects are currently unknown. CONCLUSIONS:The observed association between a schizophrenia-related neuregulin 1 gene variant and SCD may represent the first evidence of coexisting genetic susceptibility between 2 conditions that have an established clinical overlap. Further investigation is warranted to explore the molecular mechanisms of this variant in the pathogenesis of SCD.

journal_name

Heart Rhythm

journal_title

Heart rhythm

authors

Huertas-Vazquez A,Teodorescu C,Reinier K,Uy-Evanado A,Chugh H,Jerger K,Ayala J,Gunson K,Jui J,Newton-Cheh C,Albert CM,Chugh SS

doi

10.1016/j.hrthm.2013.03.020

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

994-8

issue

eissn

1547-5271

issn

1556-3871

pii

S1547-5271(13)00280-4

journal_volume

pub_type

杂志文章,多中心研究

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A common missense variant in the neuregulin 1 gene is associated with both schizophrenia and sudden cardiac death.