An interaction between NDE1 and high birth weight increases schizophrenia susceptibility.
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 DISC1 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 (>4000g) 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.
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland; Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland. Electronic address: asko.wegelius@fimnet.fi.
Asko
A
Wegelius
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland.
Maiju
M
Pankakoski
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland; Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Liisa
L
Tomppo
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland.
Ulriika
U
Lehto
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland; Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
Jouko
J
Lönnqvist
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland; Department of Social Psychiatry, Tampere School of Public Health, University of Tampere, Tampere, Finland.
Jaana
J
Suvisaari
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland; Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland; Development of Work and Work Organizations, Finnish Institute of Occupational Health, Helsinki, Finland.
Tiina
T
Paunio
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland; Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
William
W
Hennah
D000328:Adult; D000368:Aged; D001724:Birth Weight / Q000235:genetics*; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D005387:Finland / Q000453:epidemiology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D012559:Schizophrenia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*
D008869:Microtubule-Associated Proteins; C525094:Nde1 protein, human; D009419:Nerve Tissue Proteins
Birth weight; DISC1; Environment; Gene; NDE1; Neurodevelopment; Schizophrenia