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Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.
Li, Ming; Luo, Xiong-jian; Landén, Mikael; Bergen, Sarah E; Hultman, Christina M; Li, Xiao; Zhang, Wen; Yao, Yong-Gang; Zhang, Chen; Liu, Jiewei; Mattheisen, Manuel; Cichon, Sven; Mühleisen, Thomas W; Degenhardt, Franziska A; Nöthen, Markus M; Schulze, Thomas G; Grigoroiu-Serbanescu, Maria; Li, Hao; Fuller, Chris K; Chen, Chunhui; Dong, Qi; Chen, Chuansheng; Jamain, Stéphane; Leboyer, Marion; Bellivier, Frank; Etain, Bruno; Kahn, Jean-Pierre; Henry, Chantal; Preisig, Martin; Kutalik, Zoltán; Castelao, Enrique; Wright, Adam; Mitchell, Philip B; Fullerton, Janice M; Schofield, Peter R; Montgomery, Grant W; Medland, Sarah E; Gordon, Scott D; Martin, Nicholas G; Rietschel, Marcella; Liu, Chunyu; Kleinman, Joel E; Hyde, Thomas M; Weinberger, Daniel R; Su, Bing.
Afiliação
  • Li M; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Luo XJ; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Landén M; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Bergen SE; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Hultman CM; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Li X; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Zhang W; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Yao YG; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Zhang C; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Liu J; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Mattheisen M; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Cichon S; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Mühleisen TW; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Degenhardt FA; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Nöthen MM; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Schulze TG; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Grigoroiu-Serbanescu M; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Li H; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Fuller CK; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Chen C; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Dong Q; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Chen C; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Jamain S; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Leboyer M; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Bellivier F; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Etain B; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Kahn JP; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Henry C; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Preisig M; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Kutalik Z; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Castelao E; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Wright A; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Mitchell PB; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Fullerton JM; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Schofield PR; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Montgomery GW; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Medland SE; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Gordon SD; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Martin NG; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Rietschel M; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Liu C; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Kleinman JE; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Hyde TM; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Weinberger DR; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
  • Su B; Ming Li, PhD, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, USA; Xiong-jian Luo, PhD, Key Laboratory of Animal Mode
Br J Psychiatry ; 208(2): 128-37, 2016 Feb.
Article em En | MEDLINE | ID: mdl-26338991
BACKGROUND: Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. AIMS: We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. METHOD: To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals. RESULTS: Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85 × 10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54 × 10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. CONCLUSIONS: Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Bipolar / Cognição / Polimorfismo de Nucleotídeo Único / Hipocampo Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Bipolar / Cognição / Polimorfismo de Nucleotídeo Único / Hipocampo Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article