Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes.
ADHD
Mendelian randomization
causal analysis using summary effect estimates
Journal
International journal of epidemiology
ISSN: 1464-3685
Titre abrégé: Int J Epidemiol
Pays: England
ID NLM: 7802871
Informations de publication
Date de publication:
19 04 2023
19 04 2023
Historique:
received:
31
03
2021
accepted:
26
05
2022
medline:
20
4
2023
pubmed:
13
6
2022
entrez:
12
6
2022
Statut:
ppublish
Résumé
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. 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. 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]. 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.
Sections du résumé
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.
Identifiants
pubmed: 35690959
pii: 6606119
doi: 10.1093/ije/dyac128
pmc: PMC10114062
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
386-402Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.
Références
Int J Environ Res Public Health. 2021 May 06;18(9):
pubmed: 34066379
J Am Acad Child Adolesc Psychiatry. 2011 Jan;50(1):9-21
pubmed: 21156266
J Res Pers. 2008 Aug;42(4):895-913
pubmed: 19649133
Child Psychiatry Hum Dev. 2016 Jun;47(3):440-58
pubmed: 26266467
JAMA Pediatr. 2019 Mar 1;173(3):244-250
pubmed: 30688984
J Child Psychol Psychiatry. 2020 Sep;61(9):1009-1018
pubmed: 31957030
Biol Psychiatry. 2005 Jun 1;57(11):1313-23
pubmed: 15950004
JAMA Pediatr. 2022 Apr 01;176(4):384-391
pubmed: 35099540
J Child Psychol Psychiatry. 2014 May;55(5):428-35
pubmed: 24111650
Genet Epidemiol. 2016 May;40(4):304-14
pubmed: 27061298
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
Am J Epidemiol. 2013 Oct 1;178(7):1177-84
pubmed: 23863760
Int J Obes (Lond). 2019 Dec;43(12):2500-2508
pubmed: 31000774
Eur J Epidemiol. 2017 May;32(5):377-389
pubmed: 28527048
Eur Respir J. 2019 Dec 19;54(6):
pubmed: 31619474
Am J Psychiatry. 2007 Jun;164(6):942-8
pubmed: 17541055
J Pediatr Psychol. 2016 Aug;41(7):735-40
pubmed: 26717959
Int J Epidemiol. 2017 Dec 1;46(6):1985-1998
pubmed: 29040600
Mol Psychiatry. 2020 Oct;25(10):2493-2503
pubmed: 30610198
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Elife. 2018 May 30;7:
pubmed: 29846171
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
J Abnorm Child Psychol. 2011 Feb;39(2):277-91
pubmed: 20862537
Psychol Med. 2014 Jul;44(10):2223-9
pubmed: 24107258
Addict Biol. 2021 Jan;26(1):e12849
pubmed: 31733098
Nat Genet. 2018 May;50(5):668-681
pubmed: 29700475
Nat Genet. 2019 Jan;51(1):63-75
pubmed: 30478444
Commun Biol. 2018 May 3;1:36
pubmed: 30271922
Am J Med Genet B Neuropsychiatr Genet. 2021 Oct;186(7):423-429
pubmed: 32909657
J Clin Psychiatry. 2002;63 Suppl 12:10-5
pubmed: 12562056
JAMA Psychiatry. 2019 Nov 1;76(11):1141-1149
pubmed: 31389973
Nat Commun. 2020 Jul 14;11(1):3519
pubmed: 32665587
BMC Pediatr. 2012 May 14;12:50
pubmed: 22583686
Int J Epidemiol. 2015 Apr;44(2):512-25
pubmed: 26050253
Nat Genet. 2013 May;45(5):501-12
pubmed: 23563607
Nat Genet. 2018 May;50(5):693-698
pubmed: 29686387
Nat Genet. 2018 Dec;50(12):1728-1734
pubmed: 30374074
J Atten Disord. 2021 Jan;25(2):171-187
pubmed: 29806533
Atten Defic Hyperact Disord. 2017 Mar;9(1):47-65
pubmed: 27866355
Am J Epidemiol. 2021 Jun 1;190(6):1047-1055
pubmed: 33324987
Hum Mol Genet. 2014 Sep 15;23(R1):R89-98
pubmed: 25064373
Int J Epidemiol. 2017 Apr 1;46(2):409-420
pubmed: 27170763
Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012
pubmed: 30445434
Psychol Med. 2021 Aug;51(11):1890-1897
pubmed: 32249726
Nat Commun. 2018 Mar 2;9(1):905
pubmed: 29500382
Aging (Albany NY). 2017 Dec 6;9(12):2504-2520
pubmed: 29227965
Nat Genet. 2020 Jul;52(7):740-747
pubmed: 32451458
Nat Genet. 2018 Aug;50(8):1112-1121
pubmed: 30038396
PLoS One. 2013;8(3):e59742
pubmed: 23555766
Wellcome Open Res. 2019 Nov 26;4:186
pubmed: 32760811
Eur Psychiatry. 2019 Feb;56:14-34
pubmed: 30453134
Nat Genet. 2018 Jul;50(7):912-919
pubmed: 29942086
Behav Genet. 2017 May;47(3):278-289
pubmed: 28191586
Psychol Med. 2014 Jun;44(8):1779-92
pubmed: 24103255
Eur Neuropsychopharmacol. 2018 Oct;28(10):1059-1088
pubmed: 30195575
Ir J Psychol Med. 2020 Jan 24;:1-14
pubmed: 31973774
Int J Epidemiol. 2016 Dec 1;45(6):1961-1974
pubmed: 27616674
Am J Psychiatry. 2014 Mar;171(3):276-93
pubmed: 24480998
Nat Commun. 2018 Apr 16;9(1):1470
pubmed: 29662059
Eur J Epidemiol. 2018 Oct;33(10):947-952
pubmed: 30039250
Int J Epidemiol. 2021 May 17;50(2):496-509
pubmed: 33221865
Hum Mol Genet. 2019 Nov 21;28(R2):R170-R179
pubmed: 31647093
PLoS Genet. 2017 Nov 17;13(11):e1007081
pubmed: 29149188
Am J Med Genet B Neuropsychiatr Genet. 2021 Apr;186(3):140-150
pubmed: 33244849
Br J Psychiatry. 2021 Sep;219(3):507-514
pubmed: 33583444
Psychol Med. 2022 Apr;52(5):968-978
pubmed: 32762793
Nat Rev Dis Primers. 2015 Aug 06;1:15020
pubmed: 27189265
Genet Epidemiol. 2012 Apr;36(3):214-24
pubmed: 22714935