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Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder
- Source :
- Translational psychiatry, vol 7, iss 1, Translational Psychiatry
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
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.
- Subjects :
- 0301 basic medicine
Oncology
Bipolar Disorder
Genome-wide association study
Aminopeptidases
0302 clinical medicine
2.1 Biological and endogenous factors
Psychology
Pair 10
Aetiology
Genetics
Nuclear Proteins
Single Nucleotide
Serious Mental Illness
L-Type
3. Good health
Psychiatry and Mental health
Phenotype
Mental Health
Schizophrenia
Public Health and Health Services
Major depressive disorder
Original Article
Human
Ankyrins
medicine.medical_specialty
Calcium Channels, L-Type
Genotype
Clinical Sciences
BF
Schizoaffective disorder
Nerve Tissue Proteins
Polymorphism, Single Nucleotide
Genetic correlation
Chromosomes
03 medical and health sciences
Cellular and Molecular Neuroscience
Clinical Research
Internal medicine
medicine
Humans
Bipolar disorder
Allele
Polymorphism
Biological Psychiatry
Chromosomes, Human, Pair 10
Genetic heterogeneity
Human Genome
medicine.disease
R1
Brain Disorders
Cytoskeletal Proteins
030104 developmental biology
Psychotic Disorders
Case-Control Studies
RC0321
Calmodulin-Binding Proteins
Calcium Channels
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 10884920 and 21583188
- Database :
- OpenAIRE
- Journal :
- Translational psychiatry, vol 7, iss 1, Translational Psychiatry
- Accession number :
- edsair.doi.dedup.....e1c807e809575026c81766476b3f51ab