Department of Economics and Business Economics

Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language

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Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language. / Verhoef, Ellen; Demontis, Ditte; Burgess, Stephen; Shapland, Chin Yang; Dale, Philip S; Okbay, Aysu; Neale, Benjamin M; Faraone, Stephen V; iPSYCH-Broad-PGC ADHD Consortium.

In: Translational Psychiatry, Vol. 9, No. 1, 35, 2019.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Verhoef, E, Demontis, D, Burgess, S, Shapland, CY, Dale, PS, Okbay, A, Neale, BM, Faraone, SV & iPSYCH-Broad-PGC ADHD Consortium 2019, 'Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language', Translational Psychiatry, vol. 9, no. 1, 35. https://doi.org/10.1038/s41398-018-0324-2

APA

Verhoef, E., Demontis, D., Burgess, S., Shapland, C. Y., Dale, P. S., Okbay, A., ... iPSYCH-Broad-PGC ADHD Consortium (2019). Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language. Translational Psychiatry, 9(1), [35]. https://doi.org/10.1038/s41398-018-0324-2

CBE

Verhoef E, Demontis D, Burgess S, Shapland CY, Dale PS, Okbay A, Neale BM, Faraone SV, iPSYCH-Broad-PGC ADHD Consortium. 2019. Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language. Translational Psychiatry. 9(1). https://doi.org/10.1038/s41398-018-0324-2

MLA

Vancouver

Author

Verhoef, Ellen ; Demontis, Ditte ; Burgess, Stephen ; Shapland, Chin Yang ; Dale, Philip S ; Okbay, Aysu ; Neale, Benjamin M ; Faraone, Stephen V ; iPSYCH-Broad-PGC ADHD Consortium. / Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language. In: Translational Psychiatry. 2019 ; Vol. 9, No. 1.

Bibtex

@article{d8aef27e0f934e65be3c236c3047dfb5,
title = "Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language",
abstract = "Interpreting polygenic overlap between ADHD and both literacy-related and language-related impairments is challenging as genetic associations might be influenced by indirectly shared genetic factors. Here, we investigate genetic overlap between polygenic ADHD risk and multiple literacy-related and/or language-related abilities (LRAs), as assessed in UK children (N ≤ 5919), accounting for genetically predictable educational attainment (EA). Genome-wide summary statistics on clinical ADHD and years of schooling were obtained from large consortia (N ≤ 326,041). Our findings show that ADHD-polygenic scores (ADHD-PGS) were inversely associated with LRAs in ALSPAC, most consistently with reading-related abilities, and explained ≤1.6{\%} phenotypic variation. These polygenic links were then dissected into both ADHD effects shared with and independent of EA, using multivariable regressions (MVR). Conditional on EA, polygenic ADHD risk remained associated with multiple reading and/or spelling abilities, phonemic awareness and verbal intelligence, but not listening comprehension and non-word repetition. Using conservative ADHD-instruments (P-threshold < 5 × 10-8), this corresponded, for example, to a 0.35 SD decrease in pooled reading performance per log-odds in ADHD-liability (P = 9.2 × 10-5). Using subthreshold ADHD-instruments (P-threshold < 0.0015), these effects became smaller, with a 0.03 SD decrease per log-odds in ADHD risk (P = 1.4 × 10-6), although the predictive accuracy increased. However, polygenic ADHD-effects shared with EA were of equal strength and at least equal magnitude compared to those independent of EA, for all LRAs studied, and detectable using subthreshold instruments. Thus, ADHD-related polygenic links with LRAs are to a large extent due to shared genetic effects with EA, although there is evidence for an ADHD-specific association profile, independent of EA, that primarily involves literacy-related impairments.",
keywords = "ADHD SYMPTOMS, ASD, CHILDREN, COMORBIDITY, DEFICIT, HYPERACTIVITY, MENDELIAN RANDOMIZATION, READING-DISABILITY, RISK, SINGLE",
author = "Ellen Verhoef and Ditte Demontis and Stephen Burgess and Shapland, {Chin Yang} and Dale, {Philip S} and Aysu Okbay and Neale, {Benjamin M} and Faraone, {Stephen V} and {iPSYCH-Broad-PGC ADHD Consortium} and Mortensen, {Preben Bo} and Jakob Grove and Als, {Thomas Damm}",
year = "2019",
doi = "10.1038/s41398-018-0324-2",
language = "English",
volume = "9",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language

AU - Verhoef, Ellen

AU - Demontis, Ditte

AU - Burgess, Stephen

AU - Shapland, Chin Yang

AU - Dale, Philip S

AU - Okbay, Aysu

AU - Neale, Benjamin M

AU - Faraone, Stephen V

AU - iPSYCH-Broad-PGC ADHD Consortium

AU - Mortensen, Preben Bo

AU - Grove, Jakob

AU - Als, Thomas Damm

PY - 2019

Y1 - 2019

N2 - Interpreting polygenic overlap between ADHD and both literacy-related and language-related impairments is challenging as genetic associations might be influenced by indirectly shared genetic factors. Here, we investigate genetic overlap between polygenic ADHD risk and multiple literacy-related and/or language-related abilities (LRAs), as assessed in UK children (N ≤ 5919), accounting for genetically predictable educational attainment (EA). Genome-wide summary statistics on clinical ADHD and years of schooling were obtained from large consortia (N ≤ 326,041). Our findings show that ADHD-polygenic scores (ADHD-PGS) were inversely associated with LRAs in ALSPAC, most consistently with reading-related abilities, and explained ≤1.6% phenotypic variation. These polygenic links were then dissected into both ADHD effects shared with and independent of EA, using multivariable regressions (MVR). Conditional on EA, polygenic ADHD risk remained associated with multiple reading and/or spelling abilities, phonemic awareness and verbal intelligence, but not listening comprehension and non-word repetition. Using conservative ADHD-instruments (P-threshold < 5 × 10-8), this corresponded, for example, to a 0.35 SD decrease in pooled reading performance per log-odds in ADHD-liability (P = 9.2 × 10-5). Using subthreshold ADHD-instruments (P-threshold < 0.0015), these effects became smaller, with a 0.03 SD decrease per log-odds in ADHD risk (P = 1.4 × 10-6), although the predictive accuracy increased. However, polygenic ADHD-effects shared with EA were of equal strength and at least equal magnitude compared to those independent of EA, for all LRAs studied, and detectable using subthreshold instruments. Thus, ADHD-related polygenic links with LRAs are to a large extent due to shared genetic effects with EA, although there is evidence for an ADHD-specific association profile, independent of EA, that primarily involves literacy-related impairments.

AB - Interpreting polygenic overlap between ADHD and both literacy-related and language-related impairments is challenging as genetic associations might be influenced by indirectly shared genetic factors. Here, we investigate genetic overlap between polygenic ADHD risk and multiple literacy-related and/or language-related abilities (LRAs), as assessed in UK children (N ≤ 5919), accounting for genetically predictable educational attainment (EA). Genome-wide summary statistics on clinical ADHD and years of schooling were obtained from large consortia (N ≤ 326,041). Our findings show that ADHD-polygenic scores (ADHD-PGS) were inversely associated with LRAs in ALSPAC, most consistently with reading-related abilities, and explained ≤1.6% phenotypic variation. These polygenic links were then dissected into both ADHD effects shared with and independent of EA, using multivariable regressions (MVR). Conditional on EA, polygenic ADHD risk remained associated with multiple reading and/or spelling abilities, phonemic awareness and verbal intelligence, but not listening comprehension and non-word repetition. Using conservative ADHD-instruments (P-threshold < 5 × 10-8), this corresponded, for example, to a 0.35 SD decrease in pooled reading performance per log-odds in ADHD-liability (P = 9.2 × 10-5). Using subthreshold ADHD-instruments (P-threshold < 0.0015), these effects became smaller, with a 0.03 SD decrease per log-odds in ADHD risk (P = 1.4 × 10-6), although the predictive accuracy increased. However, polygenic ADHD-effects shared with EA were of equal strength and at least equal magnitude compared to those independent of EA, for all LRAs studied, and detectable using subthreshold instruments. Thus, ADHD-related polygenic links with LRAs are to a large extent due to shared genetic effects with EA, although there is evidence for an ADHD-specific association profile, independent of EA, that primarily involves literacy-related impairments.

KW - ADHD SYMPTOMS

KW - ASD

KW - CHILDREN

KW - COMORBIDITY

KW - DEFICIT

KW - HYPERACTIVITY

KW - MENDELIAN RANDOMIZATION

KW - READING-DISABILITY

KW - RISK

KW - SINGLE

UR - http://www.scopus.com/inward/record.url?scp=85060519969&partnerID=8YFLogxK

U2 - 10.1038/s41398-018-0324-2

DO - 10.1038/s41398-018-0324-2

M3 - Journal article

VL - 9

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 1

M1 - 35

ER -