Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder
Ruderfer, D. M.
Stahl, E. A.
Moran, J. L.
Belliveau, R. A.
Di Florio, Arianna
Lee, P. H.
Bromet, E. J.
Buckley, P. F.
Escamilla, M. A.
Fanous, A. H.
Fochtmann, L. J.
Lehrer, D. S.
Marder, S. R.
Morley, C. P.
Perkins, D. O.
Rakofsky, J. J.
Rapaport, M. H.
Sobell, J. L.
MetadataDangos cofnod eitem llawn
We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P = 3.28 × 10− 8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2 = 0.35; BD II SNP-h2 = 0.25; P = 0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
Charney, A W, Ruderfer, D M, Stahl, E A, Moran, J L, Chambert, K, Belliveau, R A, Forty, L, Gordon-Smith, K, Di Florio, Arianna, Lee, P H, Bromet, E J, Buckley, P F, Escamilla, M A, Fanous, A H, Fochtmann, L J, Lehrer, D S, Malaspina, D, Marder, S R, Morley, C P, Nicolini, H, Perkins, D O, Rakofsky, J J, Rapaport, M H, Medeiros, H, Sobell, J L, Green, E K, Backlund, L, Bergen, S E, Juréus, A, Schalling, M, Lichtenstein, P, Roussos, P, Knowles, J A, Jones, Ian, Jones, L A, Hultman, C M, Perlis, R H, Purcell, S M, McCarroll, S A, Pato, C N, Pato, M T, Craddock, Nicholas, Landén, M, Smoller, J W and Sklar, P (2017) 'Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder', Translational Psychiatry, 7(1), pp.e993-e993. http://dx.doi.org/10.1038/tp.2016.242
Dynodwr Gwrthrych Digidol (DOI)http://dx.doi.org/10.1038/tp.2016.242
Article published in Translational Psychiatry available open access at http://dx.doi.org/10.1038/tp.2016.242
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Genome‐wide significant locus for Research Diagnostic Criteria Schizoaffective Disorder Bipolar type Green, Elaine; Di Florio, Arianna; Forty, Liz; Gordon-Smith, Katherine; Grozeva, Detelina; Fraser, Christine; Richards, Alexander L.; Moran, Jennifer L.; Purcell, Shaun; Sklar, Pamela; Kirov, George; Owen, Michael J.; O'Donovan, Michael C.; Craddock, Nick; Jones, Lisa; Jones, Ian R. (Wiley, 2017-08-29)Studies have suggested that Research Diagnostic Criteria for Schizoaffective disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated ...
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