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Proc Biol Sci. 2014 Nov 7;281(1794):20140604. doi: 10.1098/rspb.2014.0604.

Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects.

Author information

1
Centre for Social Evolution, Department of Biology, University of Copenhagen, Copenhagen, Denmark sean.byars@unimelb.edu.au.
2
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA.
3
Centre for Social Evolution, Department of Biology, University of Copenhagen, Copenhagen, Denmark jjboomsma@bio.ku.dk.

Abstract

Opposite phenotypic and behavioural traits associated with copy number variation and disruptions to imprinted genes with parent-of-origin effects have led to the hypothesis that autism and schizophrenia share molecular risk factors and pathogenic mechanisms, but a direct phenotypic comparison of how their risks covary has not been attempted. Here, we use health registry data collected on Denmark's roughly 5 million residents between 1978 and 2009 to detect opposing risks of autism and schizophrenia depending on normal variation (mean ± 1 s.d.) in adjusted birth size, which we use as a proxy for diametric gene-dosage variation in utero. Above-average-sized babies (weight, 3691-4090 g; length, 52.8-54.3 cm) had significantly higher risk for autism spectrum (AS) and significantly lower risk for schizophrenia spectrum (SS) disorders. By contrast, below-average-sized babies (2891-3290 g; 49.7-51.2 cm) had significantly lower risk for AS and significantly higher risk for SS disorders. This is the first study directly comparing autism and schizophrenia risks in the same population, and provides the first large-scale empirical support for the hypothesis that diametric gene-dosage effects contribute to these disorders. Only the kinship theory of genomic imprinting predicts the opposing risk patterns that we discovered, suggesting that molecular research on mental disease risk would benefit from considering evolutionary theory.

KEYWORDS:

autism; birth size; copy number; genomic imprinting; parent-of-origin; schizophrenia

PMID:
25232142
PMCID:
PMC4211440
DOI:
10.1098/rspb.2014.0604
[Indexed for MEDLINE]
Free PMC Article

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