Genetically Informed Study Highlights Income-Independent Effect of Schizophrenia Liability on Mental and Physical Health DOI

Manuela R. Kouakou,

Brenda Cabrera‐Mendoza, Gita A. Pathak

et al.

Schizophrenia Bulletin, Journal Year: 2024, Volume and Issue: unknown

Published: June 7, 2024

Abstract Background and Hypothesis Individuals with schizophrenia (SCZ) suffer from comorbidities that substantially reduce their life expectancy. Socioeconomic inequalities could contribute to many of the negative health outcomes associated SCZ. Study Design We investigated genome-wide datasets related SCZ (52 017 cases 75 889 controls) Psychiatric Genomics Consortium, household income (HI; N = 361 687) UK Biobank, 2202 medical endpoints assessed in up 342 499 FinnGen participants. A phenome-wide genetic correlation analysis HI was performed, also assessing whether correlations were influenced by effect on Additionally, direct effects estimated using multivariable Mendelian randomization (MR). Results showed overlapping 70 traits (P < 2.89 × 10−5), including mental health, substance use, gastrointestinal illnesses, reproductive outcomes, liver diseases, respiratory problems, musculoskeletal phenotypes. these not affected Considering Bonferroni multiple testing correction 7.14 10−4), MR indicated may affect abortion (SCZ OR 1.07; 0.78), panic disorder 1.20; 0.60), personality disorders 1.31; 0.67), use 1.2; 0.68), adjustment 1.18; 0.78). Multivariable confirmed independent HI. Conclusions The liability physical be strongly socioeconomic differences. This suggests SCZ-specific strategies are needed affecting patients high-risk individuals.

Language: Английский

Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories DOI Creative Commons
András Gézsi, Sandra Van der Auwera, Hannu Mäkinen

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 21, 2024

Abstract The heterogeneity and complexity of symptom presentation, comorbidities genetic factors pose challenges to the identification biological mechanisms underlying complex diseases. Current approaches used identify subtypes major depressive disorder (MDD) mainly focus on clinical characteristics that cannot be linked specific models. Here, we examined multimorbidities MDD with distinct non-genetic factors. We leveraged dynamic Bayesian network determine a minimal set relevant identified seven clusters disease-burden trajectories throughout lifespan among 1.2 million participants from cohorts in UK, Finland, Spain. had clear protective- risk-factor profiles as well age-specific courses driven by inflammatory processes, comprehensive map heritability correlations these was revealed. Our results can guide development personalized treatments for based unique genetic, patients.

Language: Английский

Citations

3
Estimating the direct effects of the genetic liabilities to bipolar disorder, schizophrenia, and behavioral traits on suicide attempt using a multivariable Mendelian randomization approach DOI
Brenda Cabrera‐Mendoza,

Necla Aydin,

Gabriel R. Fries

et al.

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(9), P. 1383 - 1391

Published: Feb. 23, 2024

Language: Английский

Citations

2
MONOCLONAL ANTIBODY THERAPY IN AUTOANTIBODY-ASSOCIATED PSYCHOTIC DISORDERS AND SCHIZOPHRENIA: NARRATIVE REVIEW OF PAST AND CURRENT CLINICAL TRIALS DOI Open Access

Niels Hansen,

Berend Malchow

Psychiatria Danubina, Journal Year: 2023, Volume and Issue: 35(1), P. 8 - 15

Published: April 13, 2023

Neural cell-surface autoantibody-associated psychiatric disease and a subgroup of psychotic disorders are probably caused by an immune dysregulation such as B-cell related autoantibody production.In this review we describe past current randomized placebo-controlled trials investigating monoclonal antibodies therapy for disorders, aiming to delineate the landscape in well perspectives future trials.Rituximab ocrelizumab now being tested clinical trials, whereas initial results on tocilizumab controversial, they demonstrated cognitive-function benefit open label study schizophrenic patients -results that were not replicated trial.Adalinumab TNFalpha blockage was effective treating positive negative symptoms schizophrenia.These findings demonstrate antibody is potentially promising option treat subgroups schizophrenia patients, but it should be investigated more placebo-controlled, double-blind with large cohorts.

Language: Английский

Citations

6
Causal relationships between mood instability and autoimmune diseases: A mendelian randomization analysis DOI
Huahua Zhong, Xiao Huan,

Kexin Jiao

et al.

Autoimmunity Reviews, Journal Year: 2022, Volume and Issue: 22(1), P. 103214 - 103214

Published: Oct. 20, 2022

Language: Английский

Citations

9
Polygenic risk scores analyses of psychiatric and metabolic traits with antipsychotic-induced weight gain in schizophrenia: an exploratory study DOI
Kazunari Yoshida, Victoria S. Marshe, Samar S. M. Elsheikh

et al.

The Pharmacogenomics Journal, Journal Year: 2023, Volume and Issue: 23(5), P. 119 - 126

Published: April 27, 2023

Language: Английский

Citations

5
Blood-borne extracellular vesicles of bacteria and intestinal cells in patients with psychotic disorders DOI Creative Commons

Mette Elise Tunset,

Hanne Haslene‐Hox, Tim Van Den Bossche

et al.

Nordic Journal of Psychiatry, Journal Year: 2023, Volume and Issue: 77(7), P. 686 - 695

Published: June 24, 2023

Background Human cells and bacteria secrete extracellular vesicles (EV) which play a role in intercellular communication. EV from the host intestinal epithelium are involved regulation of bacterial gene expression growth. Bacterial (bactEV) produced intestine can pass to various tissues where they deliver biomolecules many kinds cells, including neurons. Emerging data indicate that gut microbiota is altered patients with psychotic disorders. We hypothesized amount content blood-borne bactEV would differ healthy controls.Methods analyzed for human proteins by proteomics, metaproteomic analysis, measuring level lipopolysaccharide (LPS) disorders (n = 25), tested twice, acute phase psychosis after improvement, age- sex-matched controls 25).Results Patients had lower LPS levels their compared (p .027). Metaproteome analyses confirmed finding identified Firmicutes Bacteroidetes as dominating phyla. Total amounts isolated blood was .02).Conclusions Our results suggest decreased this topic worthy further investigation given potential pathophysiological implications. Possible mechanisms involve dysregulation EV, translocation systemic circulation interact both brain immune system.

Language: Английский

Citations

5
Unique genetic and risk-factor profiles in multimorbidity clusters of depression-related disease trajectories from a study of 1.2 million subjects DOI Creative Commons
Gabriella Juhász, András Gézsi, Sandra Van der Auwera

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 2, 2023

Abstract The heterogeneity and complexity of symptom presentation, comorbidities genetic factors pose challenges to the identification biological mechanisms underlying complex diseases. Current approaches used identify subtypes major depressive disorder (MDD) mainly focus on clinical characteristics that cannot be linked specific models. Here, we examined multimorbidities MDD with distinct environmental factors. We leveraged dynamic Bayesian network determine a minimal set relevant identified seven clusters disease-burden trajectories throughout lifespan among 1.2 million participants from transnational cohorts. had clear protective- risk-factor profiles as well age-specific courses driven by inflammatory processes, comprehensive map heritability correlations these was revealed. Our results can guide development personalized treatments for based unique genetic, modifiable patients.

Language: Английский

Citations

5
Phenome-wide genetic-correlation analysis and genetically informed causal inference of amyotrophic lateral sclerosis DOI Creative Commons
Salvatore D’Antona, Gita A. Pathak, Dóra Koller

et al.

Human Genetics, Journal Year: 2023, Volume and Issue: 142(8), P. 1173 - 1183

Published: Feb. 11, 2023

Abstract Leveraging genome-wide association statistics generated from a large study of amyotrophic lateral sclerosis (ALS; 29,612 cases and 122,656 controls) UK Biobank (UKB; 4,024 phenotypes, up to 361,194 participants), we conducted phenome-wide analysis ALS genetic liability identified 46 genetically correlated traits, such as fluid intelligence score ( r g = − 0.21, p 1.74 × 10 –6 ), "spending time in pub or social club” 0.24, 2.77 non-work related walking 0.25, 1.95 college education 0.15, 7.08 –5 “ever diagnosed with panic attacks 0.39, 4.24 “self-reported other gastritis including duodenitis” 0.28, 1.4 –3 ). To assess the putative directionality these correlations, latent causal variable analysis, identifying significant causality proportions (gĉp) linking seven traits. While component duodenitis" showed effect on (gĉp 0.50, 1.26 –29 is potentially for multiple also an "ever being attacks” 0.79, 5.011 –15 ) inverse effects “other leisure/social group activities” 0.66, 1 –4 prospective memory result 0.35, 0.005). Our subsequent Mendelian randomization indicated that some associations may be due bidirectional effects. In conclusion, this investigation polygenic architecture highlights widespread pleiotropy disorder several health domains.

Language: Английский

Citations

4
Genome‐wide association studies reveal shared genetic haplotypes of autoimmune rheumatic and endocrine diseases with psychiatric disorders DOI Creative Commons
Konstantinos Voskarides,

Nefeli Giannopoulou,

Rasha Eid

et al.

Brain and Behavior, Journal Year: 2023, Volume and Issue: 13(4)

Published: March 16, 2023

Several studies have shown that autoimmune diseases are associated with psychiatric like depression and psychosis. Genetic evidence supports this association. The aim of study was to investigate if genetic variants predisposing disorders genetically linked, constructing the common haplotypes.All registered single nucleotide polymorphisms (SNPs) in Genome-wide association ("GWAS catalog") having been rheumatic endocrine were investigated for being linkage disequilibrium any disorders' SNPs. Analysis performed by LDtrait LDhap bioinformatics tools.Multiple chromosomal regions detected containing rheumatic/endocrine diseases' SNPs haplotypes constructed some these regions. Six examined here share a haplotype at HLA locus 6p21-22.Our shows linked. constructed, showing detail linkage.

Language: Английский

Citations

4
Genetic evidence for T-wave area from 12-lead electrocardiograms to monitor cardiovascular diseases in patients taking diabetes medications DOI
Mengling Qi, Haoyang Zhang,

Xuehao Xiu

et al.

Human Genetics, Journal Year: 2024, Volume and Issue: 143(9-10), P. 1095 - 1108

Published: March 20, 2024

Language: Английский

Citations

1