| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- Mullins, N., et al.
(författare)
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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| 3. |
- Li, M., et al.
(författare)
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Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance
- 2016
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 208:2, s. 128-137
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Tidskriftsartikel (refereegranskat)abstract
- Background Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 577 5) and cognitive performance (n = 342) among healthy individuals. Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P=5.85 x 10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P=3.54 x 10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
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| 4. |
- Abazov, V. M., et al.
(författare)
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Measurement of beta (t -> Wb)/beta(t -> Wq) at root s=1.96 TeV
- 2006
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 639:6, s. 616-622
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Tidskriftsartikel (refereegranskat)abstract
- We present the measurement of R = B(t -> Wb)/B(t -> Wq) in pp collisions at root s = 1.96 TeV, using 230 pb(-1) of data collected by the DO experiment at the Fermilab Tevatron Collider. We fit simultaneously R and the number (N-tt) of selected top quark pairs (tt), to the number of identified b-quark jets in events with one electron or one muon, three or more jets, and high transverse energy imbalance. To improve sensitivity, kinematical properties of events with no identified b-quark jets are included in the fit. We measure R = 1.03(-0.17)(0.19) (stat + syst), in good agreement with the standard model. We set lower limits of R > 0.61 and vertical bar V-tb vertical bar > 0.78 at 95% confidence level.
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| 5. |
- Abazov, V. M., et al.
(författare)
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Measurement of the B-s(0) lifetime using semileptonic decays
- 2006
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:24, s. 241801-
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Tidskriftsartikel (refereegranskat)abstract
- We report a measurement of the B-s(0) lifetime in the semileptonic decay channel B-s(0)-> D-s(-)mu(+)nu X (and its charge conjugate), using approximately 0.4 fb(-1) of data collected with the D0 detector during 2002-2004. Using 5176 reconstructed D-s(-)mu(+) signal events, we have measured the B-s(0) lifetime to be tau(B-s(0))=1.398 +/- 0.044(stat)(-0.025)(+0.028)(syst) ps. This is the most precise measurement of the B-s(0) lifetime to date.
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| 6. |
- Abazov, V. M., et al.
(författare)
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Measurement of the isolated photon cross section in p(p)over-bar collisions at root s=1.96 TeV
- 2006
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 639:3-4, s. 151-158
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Tidskriftsartikel (refereegranskat)abstract
- The cross section for the inclusive production of isolated photons has been measured in p (p) over bar collisions at root s = 1.96 TeV with the DO detector at the Fermilab Tevatron Collider. The photons span transverse momenta 23 to 300 GeV and have pseudorapidity vertical bar n vertical bar < 0.9. The cross section is compared with the results from two next-to-leading order perturbative QCD calculations. The theoretical predictions agree with the measurement within uncertainties.
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| 7. |
- Abazov, V. M., et al.
(författare)
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Search for a heavy resonance decaying into a Z plus jet final state in p(p)over-bar collisions at root s=1.96 TeV using the D0 detector
- 2006
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Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998 .- 1550-2368. ; 74:1, s. 011104-
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Tidskriftsartikel (refereegranskat)abstract
- We have searched for a heavy resonance decaying into a Z+jet final state in p (p) over bar collisions at a center of mass energy of 1.96 TeV at the Fermilab Tevatron collider using the D0 detector. No indication for such a resonance was found in a data sample corresponding to an integrated luminosity of 370 pb(-1). We set upper limits on the cross section times branching fraction for heavy resonance production at the 95% C.L. as a function of the resonance mass and width. The limits are interpreted within the framework of a specific model of excited quark production.
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| 8. |
- Abazov, V. M., et al.
(författare)
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Search for associated Higgs boson production WH -> WWW*-> l(+/-)nu l('+/-)nu(')+X in p(p)over-bar collisions at root S=1.96 TeV
- 2006
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:15, s. 151804-
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Tidskriftsartikel (refereegranskat)abstract
- We present a search for associated Higgs boson production in the process p (p) over bar -> WH -> WWW*-> l(+/-)nu l('+/-)nu(')+X in final states containing two like-sign isolated electrons or muons (e(+/-)e(+/-), e(+/-)mu(+/-), or mu(+/-)mu(+/-)). The search is based on D0 run II data samples corresponding to integrated luminosities of 360-380 pb(-1). No excess is observed over the predicted standard model background. We set 95% C.L. upper limits on sigma ->(p (p) over bar WH) x Br(H -> WW*) between 3.2 and 2.8 pb for Higgs boson masses from 115 to 175 GeV.
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| 9. |
- Abazov, V. M., et al.
(författare)
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Search for neutral Higgs bosons decaying to tau pairs in p(p)over-bar collisions at root s=1.96 TeV
- 2006
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:12, s. 121802-
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Tidskriftsartikel (refereegranskat)abstract
- A search for the production of neutral Higgs bosons Phi decaying into tau(+)tau(-) final states in p (p) over bar collisions at a center-of-mass energy of 1.96 TeV is presented. The data, corresponding to an integrated luminosity of approximately 325 pb(-1), were collected by the D0 experiment at the Fermilab Tevatron Collider. Since no excess compared to the expectation from standard model processes is found, limits on the production cross section times branching ratio are set. The results are combined with those obtained from the D0 search for Phi b((b) over bar)-> b (b) over barb((b) over bar) and are interpreted in the minimal supersymmetric standard model.
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| 10. |
- Abazov, V. M., et al.
(författare)
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Search for particles decaying into a Z boson and a photon in p(p)over-bar collisions at root s=1.96 TeV
- 2006
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 641:6, s. 415-422
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a search for a new particle X produced in p (p) over bar collisions at root s- = 1.96 TeV and subsequently decaying to Z gamma. The search uses 0.3 fb(-1) of data collected with the DO detector at the Fermilab Tevatron Collider. We set limits on the production cross section times the branching fraction sigma(p (p) over bar -> X) x B(X -> Z gamma) that range from 0.4 to 3.5 pb at the 95% C.L. for X with invariant masses between 100 and 1000 GeV/c(2), over a wide range of X decay widths.
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