Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study
Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study
Background: Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood. Methods: We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973–2013) and outpatient (recorded 2001–13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD. Findings: 4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18–81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50–4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42–3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60–69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors. Interpretation: This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD. Funding: Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.
774-783
Du Rietz, Ebba
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Brikell, Isabell
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Butwicka, Agnieszka
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Leone, Marica
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Chang, Zheng
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Cortese, Samuele
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D'onofrio, Brian M
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Hartman, Catharina A
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Lichtenstein, Paul
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Faraone, Stephen V
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Kuja-halkola, Ralf
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Larsson, Henrik
ab5de61d-33e6-4f87-af18-457f3818cfd4
September 2021
Du Rietz, Ebba
10cb0f63-64b1-49ef-b60c-8d483d93af17
Brikell, Isabell
8ce0666a-d578-4128-9385-20358b875b7c
Butwicka, Agnieszka
0278213c-6949-4a7f-a82e-6796977601c7
Leone, Marica
f0da264c-cb06-4a52-a045-1648a86e16e1
Chang, Zheng
46d8b0f4-85f3-4ccd-bc4e-d176843a37e2
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
D'onofrio, Brian M
c0b7aed7-382b-46e8-8256-03346bb3a5d7
Hartman, Catharina A
2a0e21ca-3f73-4558-9755-e456aba83e70
Lichtenstein, Paul
1e1573e3-7442-4d1f-969f-17dc9b7edaa4
Faraone, Stephen V
11abe086-d301-4ca2-bbd5-d7a516be924f
Kuja-halkola, Ralf
ad5f6339-6463-400d-88b1-71f8468b3c90
Larsson, Henrik
ab5de61d-33e6-4f87-af18-457f3818cfd4
Du Rietz, Ebba, Brikell, Isabell, Butwicka, Agnieszka, Leone, Marica, Chang, Zheng, Cortese, Samuele, D'onofrio, Brian M, Hartman, Catharina A, Lichtenstein, Paul, Faraone, Stephen V, Kuja-halkola, Ralf and Larsson, Henrik
(2021)
Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study.
Lancet Psychiatry, 8 (9), .
(doi:10.1016/S2215-0366(21)00171-1).
Abstract
Background: Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood. Methods: We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973–2013) and outpatient (recorded 2001–13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD. Findings: 4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18–81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50–4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42–3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60–69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors. Interpretation: This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD. Funding: Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.
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Published date: September 2021
Additional Information:
Funding Information:
HL acknowledges financial support from the Swedish Research Council (2018-02599) and the Swedish Brain Foundation (FO2018-0273). EDR was supported by the Swedish Research Council for Health, Working Life, and Welfare (2019-01172), and by Fredrik and Ingrid Thurings Stiftelse (2019-00482). ZC was supported by the Swedish Research Council for Health, Working Life, and Welfare (2019-00176). AB was supported by the Swedish Research Council (2017-00788), Stockholm County Council (clinical research appointment 20180718), and Karolinska Institutet, Strategic Research Programme in Neuroscience (StratNeuro) while working on this project. IB was supported by the Swedish Brain Foundation. ML received funding from the EU's Horizon 2020 research and innovation programme, under the Marie Sklodowska-Curie grant agreement number 721567. This project has received funding from the EU's Horizon 2020 research and innovation programme under grant agreement number 667302. SVF is supported by the EU's Seventh Framework Programme for research, technological development, and demonstration under grant agreement number 602805, the EU's Horizon 2020 research and innovation programme under grant agreement numbers 667302 and 728018, and National Institute of Mental Health grants 5R01MH101519 and U01 MH109536-01.
Funding Information:
EDR reports grants from FORTE, Ingrid and Thurings Stiftelse, during the conduct of the study; and personal speaker fees from Shire Sweden, a Takeda Pharmaceuticals company, outside of the submitted work. HL has served as a speaker for Evolan Pharma and Shire Sweden and has received research grants from Shire Sweden, outside of the submitted work. IB reports grants from The Swedish Brain Foundation, during the conduct of the study. ML reports personal fees from Johnson and Johnson, and grants from the EU's Horizon 2020, outside of the submitted work. SC reports honoraria and reimbursement for travel and accommodation expenses for lectures from the following non-profit associations: Association for Child and Adolescent Central Health, Canadian ADHD Alliance Resource, British Association of Pharmacology, and Healthcare Convention for Educational Activity on ADHD, during the conduct of the study. SVF has received income, potential income, travel expenses, or continuing education support or research support from Takeda, OnDosis, Tris, Otsuka, Arbor, Alcobra, Aveksham, Enzymotec, Neurovance, Vallon, KemPharm-Corium, Lundbeck, Ironshore, Rhodes, Akili Interactive Labs, Sunovion, Supernus, and Genomind; has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD; receives royalties from books published by Guilford Press, Oxford University Press, and Elsevier; and is programme director of www.adhdinadults.com , outside of the submitted work. All other authors declare no competing interests. EDR affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Publisher Copyright:
© 2021 Elsevier Ltd
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Local EPrints ID: 450910
URI: http://eprints.soton.ac.uk/id/eprint/450910
ISSN: 2215-0366
PURE UUID: 1f55c748-bd55-4893-9b50-349eb163efb1
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Date deposited: 20 Aug 2021 16:30
Last modified: 17 Mar 2024 03:37
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Author:
Ebba Du Rietz
Author:
Isabell Brikell
Author:
Agnieszka Butwicka
Author:
Marica Leone
Author:
Zheng Chang
Author:
Brian M D'onofrio
Author:
Catharina A Hartman
Author:
Paul Lichtenstein
Author:
Stephen V Faraone
Author:
Ralf Kuja-halkola
Author:
Henrik Larsson
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