Identification of Shared Genetic Variants Between Schizophrenia and Lung Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2018 Jan 14

PMID 29330379

Citations 17

Authors

Verena Zuber

Erik G Jonsson

Oleksandr Frei

Aree Witoelar

Wesley K Thompson

Andrew J Schork

Francesco Bettella

Yunpeng Wang

Srdjan Djurovic

Olav B Smeland

Ingrid Dieset

Ayman H Fanous

Rahul S Desikan

Sebastien Kury

Stephane Bezieau

Anders M Dale

Ian G Mills

Ole A Andreassen

Affiliations

Soon will be listed here.

Abstract

Epidemiology studies suggest associations between schizophrenia and cancer. However, the underlying genetic mechanisms are not well understood, and difficult to identify from epidemiological data. We investigated if there is a shared genetic architecture between schizophrenia and cancer, with the aim to identify specific overlapping genetic loci. First, we performed genome-wide enrichment analysis and second, we analyzed specific loci jointly associated with schizophrenia and cancer by the conjunction false discovery rate. We analyzed the largest genome-wide association studies of schizophrenia and lung, breast, prostate, ovary, and colon-rectum cancer including more than 220,000 subjects, and included genetic association with smoking behavior. Polygenic enrichment of associations with lung cancer was observed in schizophrenia, and weak enrichment for the remaining cancer sites. After excluding the major histocompatibility complex region, we identified three independent loci jointly associated with schizophrenia and lung cancer. The strongest association included nicotinic acetylcholine receptors and is an established pleiotropic locus shared between lung cancer and smoking. The two other loci were independent of genetic association with smoking. Functional analysis identified downstream pleiotropic effects on epigenetics and gene-expression in lung and brain tissue. These findings suggest that genetic factors may explain partly the observed epidemiological association of lung cancer and schizophrenia.

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