Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate.
Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the "missing heritability" of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disea...
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Public Library of Science (PLoS)
2013-04-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003455&type=printable |
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| author | Ole A Andreassen Wesley K Thompson Andrew J Schork Stephan Ripke Morten Mattingsdal John R Kelsoe Kenneth S Kendler Michael C O'Donovan Dan Rujescu Thomas Werge Pamela Sklar Psychiatric Genomics Consortium (PGC) Bipolar Disorder and Schizophrenia Working Groups J Cooper Roddey Chi-Hua Chen Linda McEvoy Rahul S Desikan Srdjan Djurovic Anders M Dale |
| author_facet | Ole A Andreassen Wesley K Thompson Andrew J Schork Stephan Ripke Morten Mattingsdal John R Kelsoe Kenneth S Kendler Michael C O'Donovan Dan Rujescu Thomas Werge Pamela Sklar Psychiatric Genomics Consortium (PGC) Bipolar Disorder and Schizophrenia Working Groups J Cooper Roddey Chi-Hua Chen Linda McEvoy Rahul S Desikan Srdjan Djurovic Anders M Dale |
| author_sort | Ole A Andreassen |
| collection | DOAJ |
| description | Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the "missing heritability" of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disease risk are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability. Epidemiological and clinical evidence suggest similar disease characteristics and overlapping genes between SCZ and BD. Here, we computed conditional Q-Q curves of data from the Psychiatric Genome Consortium (SCZ; n = 9,379 cases and n = 7,736 controls; BD: n = 6,990 cases and n = 4,820 controls) to show enrichment of SNPs associated with SCZ as a function of association with BD and vice versa with a corresponding reduction in FDR. Applying the conditional FDR method, we identified 58 loci associated with SCZ and 35 loci associated with BD below the conditional FDR level of 0.05. Of these, 14 loci were associated with both SCZ and BD (conjunction FDR). Together, these findings show the feasibility of genetic pleiotropy-informed methods to improve gene discovery in SCZ and BD and indicate overlapping genetic mechanisms between these two disorders. |
| format | Article |
| id | doaj-art-e39a2334ee69482cb4e17e06df908800 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2013-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-e39a2334ee69482cb4e17e06df9088002025-08-20T03:26:39ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-04-0194e100345510.1371/journal.pgen.1003455Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate.Ole A AndreassenWesley K ThompsonAndrew J SchorkStephan RipkeMorten MattingsdalJohn R KelsoeKenneth S KendlerMichael C O'DonovanDan RujescuThomas WergePamela SklarPsychiatric Genomics Consortium (PGC)Bipolar Disorder and Schizophrenia Working GroupsJ Cooper RoddeyChi-Hua ChenLinda McEvoyRahul S DesikanSrdjan DjurovicAnders M DaleSeveral lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the "missing heritability" of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disease risk are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability. Epidemiological and clinical evidence suggest similar disease characteristics and overlapping genes between SCZ and BD. Here, we computed conditional Q-Q curves of data from the Psychiatric Genome Consortium (SCZ; n = 9,379 cases and n = 7,736 controls; BD: n = 6,990 cases and n = 4,820 controls) to show enrichment of SNPs associated with SCZ as a function of association with BD and vice versa with a corresponding reduction in FDR. Applying the conditional FDR method, we identified 58 loci associated with SCZ and 35 loci associated with BD below the conditional FDR level of 0.05. Of these, 14 loci were associated with both SCZ and BD (conjunction FDR). Together, these findings show the feasibility of genetic pleiotropy-informed methods to improve gene discovery in SCZ and BD and indicate overlapping genetic mechanisms between these two disorders.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003455&type=printable |
| spellingShingle | Ole A Andreassen Wesley K Thompson Andrew J Schork Stephan Ripke Morten Mattingsdal John R Kelsoe Kenneth S Kendler Michael C O'Donovan Dan Rujescu Thomas Werge Pamela Sklar Psychiatric Genomics Consortium (PGC) Bipolar Disorder and Schizophrenia Working Groups J Cooper Roddey Chi-Hua Chen Linda McEvoy Rahul S Desikan Srdjan Djurovic Anders M Dale Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate. PLoS Genetics |
| title | Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate. |
| title_full | Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate. |
| title_fullStr | Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate. |
| title_full_unstemmed | Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate. |
| title_short | Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate. |
| title_sort | improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy informed conditional false discovery rate |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003455&type=printable |
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