An interaction between NDE1 and high birth weight increases schizophrenia susceptibility

PSYCHIATRY RESEARCH

卷:230

Article

Wegelius, Asko^1,2  Pankakoski, Maiju¹  Tomppo, Liisa^1,4  Lehto, Ulriika¹  Lonnqvist, Jouko^1,2  Suvisaari, Jaana^1,5  Paunio, Tiina^1,2,3,6  Hennah, William^1,4 

[1] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, FIN-00271 Helsinki, Finland

[2] Univ Helsinki, Cent Hosp, Dept Psychiat, Helsinki, Finland

[3] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland

[4] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[5] Univ Tampere, Tampere Sch Publ Hlth, Dept Social Psychiat, FIN-33101 Tampere, Finland

[6] Finnish Inst Occupat Hlth, Dev Work & Work Org, Helsinki, Finland

关键词: Birth weight;    Neurodevelopment;    Schizophrenia;    Gene;    Environment;    DISC1;    NDE1;   

DOI  :  10.1016/j.psychres.2015.08.038

来源: Elsevier

【 摘 要 】

Pre- and perinatal environmental factors have been shown to increase schizophrenia risk particularly when combined with genetic liability. The investigation of specific gene environment interactions in the etiology of psychiatric disorders has gained momentum. We used multivariate GEE regression modeling to investigate the interaction between genes of the DISCI pathway and birth weight, in relation to schizophrenia susceptibility in a Finnish schizophrenia family cohort. The study sample consisted of 457 subjects with both genotype and birth weight information. Gender and place of birth were adjusted for in the models. We found a significant interaction between birth weight and two NDE1 markers in relation to increased schizophrenia risk: a four SNP haplotype spanning NDE1 (b = 1.26, SE= 0.5, p = 0.012) and one of its constituent SNPs rs4781678 (b = 1.33, SE = 0.51, p = 0.010). Specifically, high birth weight (> 4000 g) was associated with increased schizophrenia risk among subjects homozygous for the previously identified risk alleles. The study was based on a family study sample with high genetic loading for schizophrenia and thus our findings cannot directly be generalized as representing the general population. Our results suggest that the functions mediated by NDE1 during the early stages of neurodevelopment are susceptible to the additional disruptive effects of pre- and perinatal environmental factors associated with high birth weight, augmenting schizophrenia susceptibility. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.

【 授权许可】

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