Skip to main content
eScholarship
Open Access Publications from the University of California

UC San Diego

UC San Diego Previously Published Works bannerUC San Diego

Cross-tissue eQTL enrichment of associations in schizophrenia.

  • Author(s): Bettella, Francesco
  • Brown, Andrew A
  • Smeland, Olav B
  • Wang, Yunpeng
  • Witoelar, Aree
  • Buil Demur, Alfonso A
  • Thompson, Wesley K
  • Zuber, Verena
  • Dale, Anders M
  • Djurovic, Srdjan
  • Andreassen, Ole A
  • et al.
Abstract

The genome-wide association study of the Psychiatric Genomics Consortium identified over one hundred schizophrenia susceptibility loci. The number of non-coding variants discovered suggests that gene regulation could mediate the effect of these variants on disease. Expression quantitative trait loci (eQTLs) contribute to variation in levels of mRNA. Given the co-occurrence of schizophrenia and several traits not involving the central nervous system (CNS), we investigated the enrichment of schizophrenia associations among eQTLs for four non-CNS tissues: adipose tissue, epidermal tissue, lymphoblastoid cells and blood. Significant enrichment was seen in eQTLs of all tissues: adipose (β = 0.18, p = 8.8 × 10-06), epidermal (β = 0.12, p = 3.1 × 10-04), lymphoblastoid (β = 0.19, p = 6.2 × 10-08) and blood (β = 0.19, p = 6.4 × 10-06). For comparison, we looked for enrichment of association with traits of known relevance to one or more of these tissues (body mass index, height, rheumatoid arthritis, systolic blood pressure and type-II diabetes) and found that schizophrenia enrichment was of similar scale to that observed when studying diseases in the context of a more likely causal tissue. To further investigate tissue specificity, we looked for differential enrichment of eQTLs with relevant Roadmap affiliation (enhancers and promoters) and varying distance from the transcription start site. Neither factor significantly contributed to the enrichment, suggesting that this is equally distributed in tissue-specific and cross-tissue regulatory elements. Our analyses suggest that functional correlates of schizophrenia risk are prevalent in non-CNS tissues. This could be because of pleiotropy or the effectiveness of variants affecting expression in different contexts. This suggests the utility of large, single-tissue eQTL experiments to increase eQTL discovery power in the study of schizophrenia, in addition to smaller, multiple-tissue approaches. Our results conform to the notion that schizophrenia is a systemic disorder involving many tissues.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View