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000141087 041__ $$aEnglish
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000141087 1001_ $$aPardiñas, Antonio F$$b0
000141087 245__ $$aCommon schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.
000141087 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2018
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000141087 520__ $$aSchizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.
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000141087 650_2 $$2MeSH$$aAlleles
000141087 650_2 $$2MeSH$$aCase-Control Studies
000141087 650_2 $$2MeSH$$aGene Frequency
000141087 650_2 $$2MeSH$$aGenes, Lethal: genetics
000141087 650_2 $$2MeSH$$aGenetic Loci
000141087 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000141087 650_2 $$2MeSH$$aGenome-Wide Association Study
000141087 650_2 $$2MeSH$$aHumans
000141087 650_2 $$2MeSH$$aInheritance Patterns
000141087 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000141087 650_2 $$2MeSH$$aSchizophrenia: genetics
000141087 650_2 $$2MeSH$$aSelection, Genetic
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000141087 7001_ $$0P:(DE-HGF)0$$aOwen, Michael J$$b150$$eCorresponding author
000141087 7001_ $$aPardiñas, Antonio F$$b151
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000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/1471-2156-12-64$$o10.1186/1471-2156-12-64
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng.2346$$o10.1038/ng.2346
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0028845$$o10.1371/journal.pone.0028845
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1534/genetics.114.164285$$o10.1534/genetics.114.164285
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/bioinformatics/btq340$$o10.1093/bioinformatics/btq340
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng.3211$$o10.1038/ng.3211
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/archpsyc.64.1.19$$o10.1001/archpsyc.64.1.19
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/epirev/mxn001$$o10.1093/epirev/mxn001
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng.3406$$o10.1038/ng.3406
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng.940$$o10.1038/ng.940
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/mp.2015.143$$o10.1038/mp.2015.143
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/gepi.21966$$o10.1002/gepi.21966
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/gepi.21614$$o10.1002/gepi.21614
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1146/annurev.genom.7.080505.115623$$o10.1146/annurev.genom.7.080505.115623
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nn.3922$$o10.1038/nn.3922
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/biomet/asn021$$o10.1093/biomet/asn021
000141087 999C5 $$2Crossref$$oNN Batada 2006$$y2006
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrg3934$$o10.1038/nrg3934
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/msb4100041$$o10.1038/msb4100041
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/msb.2009.27$$o10.1038/msb.2009.27
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/mp.2011.154$$o10.1038/mp.2011.154
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/hmg/ddw007$$o10.1093/hmg/ddw007
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gku1179$$o10.1093/nar/gku1179
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkv1351$$o10.1093/nar/gkv1351
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkv1070$$o10.1093/nar/gkv1070
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gku1205$$o10.1093/nar/gku1205
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrg.2016.29$$o10.1038/nrg.2016.29
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkv1189$$o10.1093/nar/gkv1189
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ajmg.b.32135$$o10.1002/ajmg.b.32135
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/molbev/msv031$$o10.1093/molbev/msv031
000141087 999C5 $$2Crossref$$oBF Voight 2006$$y2006
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nature06250$$o10.1038/nature06250
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2013.01.035$$o10.1016/j.cell.2013.01.035
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nature12961$$o10.1038/nature12961
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.1124309$$o10.1126/science.1124309
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1534/genetics.113.152587$$o10.1534/genetics.113.152587
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1017/S0016672300033619$$o10.1017/S0016672300033619
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1146/annurev-genom-091212-153509$$o10.1146/annurev-genom-091212-153509
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/bioinformatics/btt730$$o10.1093/bioinformatics/btt730
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gku1010$$o10.1093/nar/gku1010
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nature09298$$o10.1038/nature09298
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/molbev/msv172$$o10.1093/molbev/msv172
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng.3216$$o10.1038/ng.3216
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00737-002-0142-6$$o10.1007/s00737-002-0142-6
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00125-010-2003-6$$o10.1007/s00125-010-2003-6
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1177/0956797612439067$$o10.1177/0956797612439067
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/bioinformatics/btw613$$o10.1093/bioinformatics/btw613
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng.2802$$o10.1038/ng.2802
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/mp.2016.49$$o10.1038/mp.2016.49
000141087 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng.2897$$o10.1038/ng.2897