Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function

Schizophrenia Bulletin
Xiong-Jian LuoYong-Gang Yao

Abstract

Genome-wide association studies have identified multiple risk variants and loci that show robust association with schizophrenia. Nevertheless, it remains unclear how these variants confer risk to schizophrenia. In addition, the driving force that maintains the schizophrenia risk variants in human gene pool is poorly understood. To investigate whether expression-associated genetic variants contribute to schizophrenia susceptibility, we systematically integrated brain expression quantitative trait loci and genome-wide association data of schizophrenia using Sherlock, a Bayesian statistical framework. Our analyses identified ZNF323 as a schizophrenia risk gene (P = 2.22×10(-6)). Subsequent analyses confirmed the association of the ZNF323 and its expression-associated single nucleotide polymorphism rs1150711 in independent samples (gene-expression: P = 1.40×10(-6); single-marker meta-analysis in the combined discovery and replication sample comprising 44123 individuals: P = 6.85×10(-10)). We found that the ZNF323 was significantly downregulated in hippocampus and frontal cortex of schizophrenia patients (P = .0038 and P = .0233, respectively). Evidence for pleiotropic effects was detected (association of rs1150711 with lung functio...Continue Reading

References

Jan 1, 1997·Journal of Psychopharmacology·M B Knable, D R Weinberger
Jun 30, 2001·The American Journal of Psychiatry·W M PerlsteinJ D Cohen
Jul 31, 2002·Biochemical and Biophysical Research Communications·Hualiang PiMingyao Liu
Oct 17, 1964·Nature·J HUXLEYA HOFFER
Dec 10, 2003·Archives of General Psychiatry·Patrick F SullivanMichael C Neale
Dec 20, 2003·Nature·UNKNOWN International HapMap Consortium
Jul 21, 2004·Molecular Psychiatry·P J Harrison, D R Weinberger
Jun 22, 2005·Cellular and Molecular Life Sciences : CMLS·P J Wittkopp
Feb 24, 2006·PLoS Biology·Benjamin F VoightJonathan K Pritchard
Jul 17, 2007·Journal of Inherited Metabolic Disease·B Nørgaard-Pedersen, D M Hougaard
Aug 7, 2007·PLoS Genetics·Bertrand Servin, Matthew Stephens
Sep 6, 2007·Proceedings. Biological Sciences·Bernard CrespiSteve Dorus
Nov 6, 2007·Nature Genetics·Amanda J MyersJohn Hardy
Nov 24, 2007·Schizophrenia Bulletin·Godfrey D Pearlson, Bradley S Folley
Mar 13, 2008·Schizophrenia Bulletin·Nicholas J Bray
Aug 5, 2008·Nature Genetics·Michael C O'DonovanUNKNOWN Molecular Genetics of Schizophrenia Collaboration
Oct 15, 2008·Human Molecular Genetics·Paul I W de BakkerBenjamin F Voight
Mar 25, 2009·Genome Research·Joseph K PickrellJonathan K Pritchard
May 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lucia A HindorffTeri A Manolio
Jul 3, 2009·Nature·Hreinn StefanssonDavid A Collier
Jul 3, 2009·Nature·UNKNOWN International Schizophrenia ConsortiumPamela Sklar
Jul 7, 2009·BMC Genomics·Mads V HollegaardDavid M Hougaard
Sep 8, 2009·BMC Evolutionary Biology·Feng ChengChangqing Zeng
Sep 3, 2010·Genetica·Hong Li, Hongwen Deng
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Aug 4, 2011·Scandinavian Journal of Public Health·Ole MorsPreben Bo Mortensen
Sep 20, 2011·Nature Genetics·UNKNOWN Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium
Oct 28, 2011·Nature·Hyo Jung KangNenad Sestan
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium

❮ Previous
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Citations

Jun 18, 2016·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Jiewei LiuBing Su
Jul 28, 2016·Schizophrenia Bulletin·Yong WuXiong-Jian Luo
Sep 3, 2016·Neuroscience Letters·Zhimin RenShuquan Rao
Sep 20, 2016·Journal of Psychiatric Research·Yong-Xia HuoXiong-Jian Luo
Feb 28, 2018·Nature Communications·Cui-Ping YangXiong-Jian Luo
Jan 31, 2019·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·I K MalashenkovaN A Didkovsky
Feb 17, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Huijuan LiMing Li
Oct 7, 2017·Molecular Genetics and Genomics : MGG·Yunyan HeQiang Liu
Jun 24, 2017·Genetics·Yuelong GuoDahlia M Nielsen
Feb 10, 2019·Nature Communications·Yongxia HuoXiong-Jian Luo
Jul 3, 2019·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Lingfei LiuRanran Song
Feb 2, 2021·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Shiwu LiXiong-Jian Luo
Mar 5, 2021·Scientific Reports·Yung-Che ChenUNKNOWN Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group
Mar 27, 2021·PLoS Genetics·Kun WangSridhar Hannenhalli
Sep 10, 2020·Journal of Medical Genetics·Yan ZhangXiongJian Luo
Dec 24, 2021·Frontiers in Molecular Neuroscience·Jianbin DuKazuya Iwamoto

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