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Improved Detection of Common Variants Associated with Schizophrenia and Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate
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نویسنده
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andreassen o.a. ,thompson w.k. ,schork a.j. ,ripke s. ,mattingsdal m. ,kelsoe j.r. ,kendler k.s. ,o'donovan m.c. ,rujescu d. ,werge t. ,sklar p. ,roddey j.c. ,chen c.-h. ,mcevoy l. ,desikan r.s. ,djurovic s. ,dale a.m.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 4
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چکیده
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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. © 2013 andreassen et al.
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آدرس
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kg jebsen centre for psychosis research,institute of clinical medicine,university of oslo,oslo,norway,division of mental health and addiction,oslo university hospital,oslo,norway,department of psychiatry,university of california san diego,la jolla,ca, United States, department of psychiatry,university of california san diego,la jolla,ca, United States, multimodal imaging laboratory,university of california san diego,la jolla,ca,united states,cognitive sciences graduate program,university of california san diego,la jolla,ca,united states,center for human development,university of california san diego,la jolla,ca, United States, center for human genetic research,massachusetts general hospital,boston,ma, United States, kg jebsen centre for psychosis research,institute of clinical medicine,university of oslo,oslo, Norway, department of psychiatry,university of california san diego,la jolla,ca, United States, virginia institute for psychiatric and behavioral genetics,department of psychiatry,virginia commonwealth university,richmond,va, United States, mrc centre for neuropsychiatric genetics and genomics,school of medicine,cardiff university,heath park,cardiff, United Kingdom, department of psychiatry,university of halle-wittenberg,halle, Germany, institute of biological psychiatry,mhc,sct. hans,university of copenhagen,copenhagen, Denmark, the division of psychiatric genetics and genomics,mount sinai school of medicine,new york,ny, United States, multimodal imaging laboratory,university of california san diego,la jolla,ca,united states,department of radiology,university of california san diego,la jolla,ca, United States, department of psychiatry,university of california san diego,la jolla,ca,united states,multimodal imaging laboratory,university of california san diego,la jolla,ca, United States, multimodal imaging laboratory,university of california san diego,la jolla,ca,united states,department of radiology,university of california san diego,la jolla,ca, United States, multimodal imaging laboratory,university of california san diego,la jolla,ca,united states,department of radiology,university of california san diego,la jolla,ca, United States, kg jebsen centre for psychosis research,institute of clinical medicine,university of oslo,oslo,norway,division of mental health and addiction,oslo university hospital,oslo, Norway, department of psychiatry,university of california san diego,la jolla,ca,united states,multimodal imaging laboratory,university of california san diego,la jolla,ca,united states,department of radiology,university of california san diego,la jolla,ca,united states,department of neurosciences,university of california san diego,la jolla,ca, United States
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Authors
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