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Gene expression in skin and lymphoblastoid cells: Refined statistical method reveals extensive overlap in cis-eQTL signals
Authors:Ding Jun  Gudjonsson Johann E  Liang Liming  Stuart Philip E  Li Yun  Chen Wei  Weichenthal Michael  Ellinghaus Eva  Franke Andre  Cookson William  Nair Rajan P  Elder James T  Abecasis Gonçalo R
Institution:1 Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA
2 Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
3 Department of Dermatology, University of Kiel, Kiel D-24105, Germany
4 Institute for Clinical Molecular Biology, University of Kiel, Kiel D-24105, Germany
5 National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
6 Department of Dermatology, Ann Arbor VA Health System, Ann Arbor, MI 48109, USA
Abstract:Psoriasis, an immune-mediated, inflammatory disease of the skin and joints, provides an ideal system for expression quantitative trait locus (eQTL) analysis, because it has a strong genetic basis and disease-relevant tissue (skin) is readily accessible. To better understand the role of genetic variants regulating cutaneous gene expression, we identified 841 cis-acting eQTLs using RNA extracted from skin biopsies of 53 psoriatic individuals and 57 healthy controls. We found substantial overlap between cis-eQTLs of normal control, uninvolved psoriatic, and lesional psoriatic skin. Consistent with recent studies and with the idea that control of gene expression can mediate relationships between genetic variants and disease risk, we found that eQTL SNPs are more likely to be associated with psoriasis than are randomly selected SNPs. To explore the tissue specificity of these eQTLs and hence to quantify the benefits of studying eQTLs in different tissues, we developed a refined statistical method for estimating eQTL overlap and used it to compare skin eQTLs to a published panel of lymphoblastoid cell line (LCL) eQTLs. Our method accounts for the fact that most eQTL studies are likely to miss some true eQTLs as a result of power limitations and shows that ~70% of cis-eQTLs in LCLs are shared with skin, as compared with the naive estimate of < 50% sharing. Our results provide a useful method for estimating the overlap between various eQTL studies and provide a catalog of cis-eQTLs in skin that can facilitate efforts to understand the functional impact of identified susceptibility variants on psoriasis and other skin traits.
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