A genome-wide association study of bipolar disorder in Norwegian individuals, followed by replication in Icelandic sample

Djurovic, Srdjan; Gústafsson, Ómar; Mattingsdal, Morten; Athanasiu, Lavinia; Bjella, Thomas; Tesli, Martin; Agartz, Ingrid; Lorentzen, Steinar; Melle, Ingrid; Morken, Gunnar; Andreassen, Ole A.

doi:10.1016/j.jad.2010.04.007

Cited by 105 publications

(85 citation statements)

References 22 publications

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“…Overall, the observed associations replicated weakly and inconsistently; however, given the sample size limitations and the vicinity of genes that are strong functional candidates, these results warrant attention for future genetic and functional studies. The marker showing the strongest association with sustained attention/vigilance, which surpassed genome‐wide significance cut‐off, is of potential interest since it is located within a brain expressed gene ( CNTNAP5 ) previously implicated in neuropsychiatric diseases with known disturbances in sustained attention, that is bipolar disorder, autism and attention‐deficit hyperactivity disorder [Djurovic S et al, 2010; Pagnamenta AT et al, 2010; Neale BM et al, 2010 ] . CNTNAP5 protein belongs to the neurexin superfamily of cell‐adhesion molecules, which have been shown to constitute key regulators of synapse formation and neurotransmission [Anderson GR et al, 2012; Karayannis T et al, 2014].…”

Section: Discussionmentioning

confidence: 99%

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Hatzimanolis

Bhatnagar

Moes

et al. 2015

American J of Med Genetics Pt B

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Neurocognitive abilities constitute complex traits with considerable heritability. Impaired neurocognition is typically observed in schizophrenia (SZ), whereas convergent evidence has shown shared genetic determinants between neurocognition and SZ. Here, we report a genome‐wide association study (GWAS) on neuropsychological and oculomotor traits, linked to SZ, in a general population sample of healthy young males (n = 1079). Follow‐up genotyping was performed in an identically phenotyped internal sample (n = 738) and an independent cohort of young males with comparable neuropsychological measures (n = 825). Heritability estimates were determined based on genome‐wide single‐nucleotide polymorphisms (SNPs) and potential regulatory effects on gene expression were assessed in human brain. Correlations with general cognitive ability and SZ risk polygenic scores were tested utilizing meta‐analysis GWAS results by the Cognitive Genomics Consortium (COGENT) and the Psychiatric Genomics Consortium (PGC‐SZ). The GWAS results implicated biologically relevant genetic loci encoding protein targets involved in synaptic neurotransmission, although no robust individual replication was detected and thus additional validation is required. Secondary permutation‐based analysis revealed an excess of strongly associated loci among GWAS top‐ranked signals for verbal working memory (WM) and antisaccade intra‐subject reaction time variability (empirical P < 0.001), suggesting multiple true‐positive single‐SNP associations. Substantial heritability was observed for WM performance. Further, sustained attention/vigilance and WM were suggestively correlated with both COGENT and PGC‐SZ derived polygenic scores. Overall, these results imply that common genetic variation explains some of the variability in neurocognitive functioning among young adults, particularly WM, and provide supportive evidence that increased SZ genetic risk predicts neurocognitive fluctuations in the general population. © 2015 The Authors American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Hatzimanolis

Bhatnagar

Moes

et al. 2015

American J of Med Genetics Pt B

View full text Add to dashboard Cite

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“…The CTR sample (N ¼414) was randomly drawn from the statistical population registers of the same areas of Oslo as the patients and was contacted by mail. The entire sample consisted of Northern European Caucasians, mainly Norwegians, previously demonstrated to be genetically homogenous Djurovic et al, 2010). General exclusion criteria were hospitalized head injury, neurological disorder, unstable or uncontrolled medical condition that interferes with brain function and/or an IQ below 70.…”

Section: Participantsmentioning

confidence: 99%

Polygenic risk scores in bipolar disorder subgroups

Aminoff

Tesli

Bettella

et al. 2015

Journal of Affective Disorders

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“…Microtubule and microfibril-related mechanisms need to remain stabilized in order to provide accurate neuronal migration and function; disrupted circuits of molecular signalling chain in the brain may cause improper synapse formation, synaptic transmission, and synaptic plasticity that ultimately may end up with BPD [10]. A recent genome-wide association study based on single-nucleotide polymorphisms indicated that polymorphic FBN1 leads to susceptibility to BPD [11].…”

Section: Discussionmentioning

confidence: 99%

Bipolar disorder with Marfan syndrome: a case illustration based on possible involvement of TGF-β1 in the common etiopathogenesis

Balcıoğlu

Kırlıoğlu

Özgen

2017

Psychiatry and Clinical Psychopharmacology

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A genome-wide association study of bipolar disorder in Norwegian individuals, followed by replication in Icelandic sample

Cited by 105 publications

References 22 publications

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Polygenic risk scores in bipolar disorder subgroups

Bipolar disorder with Marfan syndrome: a case illustration based on possible involvement of TGF-β1 in the common etiopathogenesis

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