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Open Access Highly Accessed Research article

Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation

Roberto Amato123*, Michele Pinelli14, Antonella Monticelli5, Gennaro Miele123 and Sergio Cocozza14

Author Affiliations

1 Gruppo Interdipartimentale di Bioinformatica e Biologia Computazionale, Università di Napoli "Federico II" - Università di Salerno, Naples, Italy

2 Dipartimento di Scienze Fisiche, Università degli Studi di Napoli "Federico II", Naples, Italy

3 Istituto Nazionale di Fisica Nucleare - Sezione di Napoli, Naples, Italy

4 Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano", Università degli Studi di Napoli "Federico II", Naples, Italy

5 Istituto di Endocrinologia ed Oncologia Sperimentale, CNR Napoli, Naples, Italy

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BMC Evolutionary Biology 2010, 10:351  doi:10.1186/1471-2148-10-351

Published: 11 November 2010

Abstract

Background

Many natural phenomena are directly or indirectly related to latitude. Living at different latitudes, indeed, has its consequences with being exposed to different climates, diets, light/dark cycles, etc. In humans, one of the best known examples of genetic traits following a latitudinal gradient is skin pigmentation. Nevertheless, also several diseases show latitudinal clinals such as hypertension, cancer, dismetabolic conditions, schizophrenia, Parkinson's disease and many more.

Results

We investigated, for the first time on a wide genomic scale, the latitude-driven adaptation phenomena. In particular, we selected a set of genes showing signs of latitude-dependent population differentiation. The biological characterization of these genes showed enrichment for neural-related processes. In light of this, we investigated whether genes associated to neuropsychiatric diseases were enriched by Latitude-Related Genes (LRGs). We found a strong enrichment of LRGs in the set of genes associated to schizophrenia. In an attempt to try to explain this possible link between latitude and schizophrenia, we investigated their associations with vitamin D. We found in a set of vitamin D related genes a significant enrichment of both LRGs and of genes involved in schizophrenia.

Conclusions

Our results suggest a latitude-driven adaptation for both schizophrenia and vitamin D related genes. In addition we confirm, at a molecular level, the link between schizophrenia and vitamin D. Finally, we discuss a model in which schizophrenia is, at least partly, a maladaptive by-product of latitude dependent adaptive changes in vitamin D metabolism.