Socioeconomic status and severe mental disorders: A Bidirectional Multivariable Mendelian Randomisation Study DOI Creative Commons
Álvaro Andreu-Bernabeu, Javier González‐Peñas, Celso Arango

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 3, 2023

Abstract Importance Despite the evidence supporting relationship between socioeconomic status (SES) and severe mental disorders (SMD), directionality of associations income or education is still poorly understood. Objective To investigate potential bidirectional causal relationships genetic liability to two main components SES (i.e., educational attainment (EA)) on three SMD: schizophrenia (SCZ), bipolar disorder (BD) major depressive (MDD) using multivariable Mendelian randomisation. Design, Setting, Participants We performed a bidirectional, two-sample randomisation (MVMR) study summary statistics from latest genome-wide studies (GWAS) Psychiatric Genomics Consortium (PGC), UK biobank Social Science Genetic Association (SSGAC) dissect EA with schizophrenia, BD MDD including data for participants European ancestry only. Data covered September 2022 January 2023. Main Outcomes Measures Socioeconomic phenotypes (household biobank, n=397,751, based largest meta-analysis GWAS individuals ancestry, n=766,345) SMD PGC (schizophrenia, n=127,906; BD, n=51,710; n=500,119). Follow-up analyses were intelligence meta-analytical phenotype, n=269,867. Results derived included in Biobank, SSGAC consortiums (samples ranging 766,345 51,710 individuals). Univariable MR (UVMR) showed that household was associated decreased risk (IVW-ORSCZ=0.58 per-one-SD increase; P-value= 0.016) (IVW-ORMDD:0.66 P-value: 9.81e-08), smaller reverse effect (IVW-βSCZ= -0.1147, P-value=7.55E-08; IVW-βDEP=-0.0356, P-value=8.70E-04). Direct effects after adjusting comparable. UVMR lower higher no significant schizophrenia. After accounting MMVR analyses, direct increased (MVMR-ORBIP: 2.69 per SD increase, 0.0000113) (MVMR-ORSCZ: 2.09 per-SD-increase, 0.00108), but not MDD. Effects association larger when MVMR model, thus suggesting they might reflect non-cognitive component. Conclusions Relevance The findings this analysis suggest an heterogenous pattern links SMD. found negative On contrary, we positive disorder, which only becomes apparent income. These shed light directional mechanisms social determinants may help guide public health strategies addressing inequality economic disadvantages.

Language: Английский

The genetics of cognition in schizophrenia DOI
Michael J. Owen, Michael O’Donovan

Genomic psychiatry :, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 8

Published: July 16, 2024

This conceptual review focuses on recent insights into the nature of relationship between genetic predisposition and cognitive impairment as risk factors for schizophrenia, that influence degree in those with disorder. There is clear evidence premorbid frequently present who develop and, across range abilities, poorer cognition associated higher liability to Evidence from population studies strongly supports hypothesis a marker underlying neurodevelopmental disorder, rather than prodromal manifestation. The deficit seems be largely explained by non-familial familial jointly schizophrenia ability, these appear act sensitize individuals risk. also may better indexed which ability deviates expectations per se . Premorbid thus does not itself lie causal pathway it abnormality substantially non-familial, increases schizophrenia. Genetic factors, including both common rare alleles, IQ general contribute further decline function after diagnosis some well an increased dementia. reflect substantial shared heritability neurodegenerative disorders, but causes postonset its pathophysiology remain uncertain.

Language: Английский

Citations

0
Socioeconomic status and severe mental disorders: A Bidirectional Multivariable Mendelian Randomisation Study DOI Creative Commons
Álvaro Andreu-Bernabeu, Javier González‐Peñas, Celso Arango

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 3, 2023

Abstract Importance Despite the evidence supporting relationship between socioeconomic status (SES) and severe mental disorders (SMD), directionality of associations income or education is still poorly understood. Objective To investigate potential bidirectional causal relationships genetic liability to two main components SES (i.e., educational attainment (EA)) on three SMD: schizophrenia (SCZ), bipolar disorder (BD) major depressive (MDD) using multivariable Mendelian randomisation. Design, Setting, Participants We performed a bidirectional, two-sample randomisation (MVMR) study summary statistics from latest genome-wide studies (GWAS) Psychiatric Genomics Consortium (PGC), UK biobank Social Science Genetic Association (SSGAC) dissect EA with schizophrenia, BD MDD including data for participants European ancestry only. Data covered September 2022 January 2023. Main Outcomes Measures Socioeconomic phenotypes (household biobank, n=397,751, based largest meta-analysis GWAS individuals ancestry, n=766,345) SMD PGC (schizophrenia, n=127,906; BD, n=51,710; n=500,119). Follow-up analyses were intelligence meta-analytical phenotype, n=269,867. Results derived included in Biobank, SSGAC consortiums (samples ranging 766,345 51,710 individuals). Univariable MR (UVMR) showed that household was associated decreased risk (IVW-ORSCZ=0.58 per-one-SD increase; P-value= 0.016) (IVW-ORMDD:0.66 P-value: 9.81e-08), smaller reverse effect (IVW-βSCZ= -0.1147, P-value=7.55E-08; IVW-βDEP=-0.0356, P-value=8.70E-04). Direct effects after adjusting comparable. UVMR lower higher no significant schizophrenia. After accounting MMVR analyses, direct increased (MVMR-ORBIP: 2.69 per SD increase, 0.0000113) (MVMR-ORSCZ: 2.09 per-SD-increase, 0.00108), but not MDD. Effects association larger when MVMR model, thus suggesting they might reflect non-cognitive component. Conclusions Relevance The findings this analysis suggest an heterogenous pattern links SMD. found negative On contrary, we positive disorder, which only becomes apparent income. These shed light directional mechanisms social determinants may help guide public health strategies addressing inequality economic disadvantages.

Language: Английский

Citations

0