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Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational a...

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Autores principales: Soler Artigas, María, Sánchez-Mora, Cristina, Rovira, Paula, Vilar-Ribó, Laura, Ramos-Quiroga, Josep Antoni, Ribasés, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10114062/
https://www.ncbi.nlm.nih.gov/pubmed/35690959
http://dx.doi.org/10.1093/ije/dyac128
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author Soler Artigas, María
Sánchez-Mora, Cristina
Rovira, Paula
Vilar-Ribó, Laura
Ramos-Quiroga, Josep Antoni
Ribasés, Marta
author_facet Soler Artigas, María
Sánchez-Mora, Cristina
Rovira, Paula
Vilar-Ribó, Laura
Ramos-Quiroga, Josep Antoni
Ribasés, Marta
author_sort Soler Artigas, María
collection PubMed
description BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits. METHODS: We used genome-wide association study (GWAS) summary statistics for ADHD (n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD, we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results. RESULTS: Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR) = 0.966, 95% credible interval (CrI) = (0.954, 0.979)] and increased lifetime number of sexual partners [OR = 1.023, 95% CrI = (1.013, 1.033)]. We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), respectively] and time spent watching television [OR = 1.862, 95% CrI = (1.545, 2.246)], and evidence for a bidirectional effect for age of first sexual intercourse [beta = −0.058, 95% CrI = (−0.072, −0.044) and OR = 0.413, 95% CrI = (0.372, 0.457), respectively], odds of decreased age completed full-time education [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533), respectively] and years of schooling [beta = -0.036, 95% CrI = (−0.048, −0.024) and OR = 0.458, 95% CrI = (0.411, 0.511), respectively]. CONCLUSIONS: Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories.
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spelling pubmed-101140622023-04-20 Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes Soler Artigas, María Sánchez-Mora, Cristina Rovira, Paula Vilar-Ribó, Laura Ramos-Quiroga, Josep Antoni Ribasés, Marta Int J Epidemiol ADHD and Autism Spectrum Disorder BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits. METHODS: We used genome-wide association study (GWAS) summary statistics for ADHD (n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD, we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results. RESULTS: Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR) = 0.966, 95% credible interval (CrI) = (0.954, 0.979)] and increased lifetime number of sexual partners [OR = 1.023, 95% CrI = (1.013, 1.033)]. We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), respectively] and time spent watching television [OR = 1.862, 95% CrI = (1.545, 2.246)], and evidence for a bidirectional effect for age of first sexual intercourse [beta = −0.058, 95% CrI = (−0.072, −0.044) and OR = 0.413, 95% CrI = (0.372, 0.457), respectively], odds of decreased age completed full-time education [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533), respectively] and years of schooling [beta = -0.036, 95% CrI = (−0.048, −0.024) and OR = 0.458, 95% CrI = (0.411, 0.511), respectively]. CONCLUSIONS: Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories. Oxford University Press 2022-06-12 /pmc/articles/PMC10114062/ /pubmed/35690959 http://dx.doi.org/10.1093/ije/dyac128 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle ADHD and Autism Spectrum Disorder
Soler Artigas, María
Sánchez-Mora, Cristina
Rovira, Paula
Vilar-Ribó, Laura
Ramos-Quiroga, Josep Antoni
Ribasés, Marta
Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes
title Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes
title_full Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes
title_fullStr Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes
title_full_unstemmed Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes
title_short Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes
title_sort mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes
topic ADHD and Autism Spectrum Disorder
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10114062/
https://www.ncbi.nlm.nih.gov/pubmed/35690959
http://dx.doi.org/10.1093/ije/dyac128
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