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.
['Wegelius|Asko|A|', 'Pankakoski|Maiju|M|', 'Tomppo|Liisa|L|', 'Lehto|Ulriika|U|', 'Lönnqvist|Jouko|J|', 'Suvisaari|Jaana|J|', 'Paunio|Tiina|T|', 'Hennah|William|W|']
D000328:Adult D000368:Aged D001724:Birth Weight D015331:Cohort Studies D004198:Disease Susceptibility D005260:Female D005387:Finland D006239:Haplotypes D006801:Humans D008297:Male D008869:Microtubule-Associated Proteins D008875:Middle Aged D009419:Nerve Tissue Proteins D020641:Polymorphism, Single Nucleotide D012189:Retrospective Studies D012559:Schizophrenia
NDE1 Birth weight Schizophrenia Gene Environment DISC1 Neurodevelopment