Abstract
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.
Original language | English (US) |
---|---|
Article number | e993 |
Journal | Translational Psychiatry |
Volume | 7 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2017 |
Fingerprint
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Biological Psychiatry
Cite this
Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder. / Charney, A. W.; Ruderfer, D. M.; Stahl, E. A.; Moran, J. L.; Chambert, K.; Belliveau, R. A.; Forty, L.; Gordon-Smith, K.; Di Florio, A.; Lee, P. H.; Bromet, E. J.; Buckley, Peter 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, I.; Jones, L. A.; Hultman, C. M.; Perlis, R. H.; Purcell, S. M.; McCarroll, S. A.; Pato, C. N.; Pato, M. T.; Craddock, N.; Landén, M.; Smoller, J. W.; Sklar, P.
In: Translational Psychiatry, Vol. 7, No. 1, e993, 01.01.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder
AU - Charney, A. W.
AU - Ruderfer, D. M.
AU - Stahl, E. A.
AU - Moran, J. L.
AU - Chambert, K.
AU - Belliveau, R. A.
AU - Forty, L.
AU - Gordon-Smith, K.
AU - Di Florio, A.
AU - Lee, P. H.
AU - Bromet, E. J.
AU - Buckley, Peter F
AU - Escamilla, M. A.
AU - Fanous, A. H.
AU - Fochtmann, L. J.
AU - Lehrer, D. S.
AU - Malaspina, D.
AU - Marder, S. R.
AU - Morley, C. P.
AU - Nicolini, H.
AU - Perkins, D. O.
AU - Rakofsky, J. J.
AU - Rapaport, M. H.
AU - Medeiros, H.
AU - Sobell, J. L.
AU - Green, E. K.
AU - Backlund, L.
AU - Bergen, S. E.
AU - Juréus, A.
AU - Schalling, M.
AU - Lichtenstein, P.
AU - Roussos, P.
AU - Knowles, J. A.
AU - Jones, I.
AU - Jones, L. A.
AU - Hultman, C. M.
AU - Perlis, R. H.
AU - Purcell, S. M.
AU - McCarroll, S. A.
AU - Pato, C. N.
AU - Pato, M. T.
AU - Craddock, N.
AU - Landén, M.
AU - Smoller, J. W.
AU - Sklar, P.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85020912677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020912677&partnerID=8YFLogxK
U2 - 10.1038/tp.2016.242
DO - 10.1038/tp.2016.242
M3 - Article
C2 - 28072414
AN - SCOPUS:85020912677
VL - 7
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - e993
ER -