TY - JOUR
T1 - Do ADHD-Impulsivity and BMI have shared polygenic and neural correlates?
AU - Barker, Edward
AU - Ing, Alex James
AU - Biondo, Francesca
AU - Jia, Tianye
AU - Pingault, Jean-Baptiste
AU - Du Rietz, Ebba Eva Charlotte
AU - Zhang, Yuning
AU - Ruggeri, Barbara
AU - Banaschewski, Tobias
AU - Hohmann, Sarah
AU - Bokde, Arun Lw
AU - Bromberg, Uli
AU - Büchel, Christian
AU - Quinlan, Erin Burke
AU - Barke, Edmund James
AU - Bowling , April B.
AU - Desrivieres, Sylvane
AU - Flor, Herta
AU - Frouin, Vincent
AU - Garavan, Hugh
AU - Gowland, Penny
AU - Heinz, Andreas
AU - Ittermann, Bernd
AU - Martinot, Jean-Luc
AU - Martinot, Marie Laure Paillère
AU - Nees, Frauke
AU - Papadopoulos Orfanos, Dimitri
AU - Poustka, Luise
AU - Smolka, Michael N.
AU - Vetter, Nora C.
AU - Walter, Henrik
AU - Whelan, Robert
AU - Schumann, Gunter
AU - Asherson, Philip
PY - 2019/6/21
Y1 - 2019/6/21
N2 - There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5x10-6 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.06, 90% CIs = 0.001, 0.019) and BMI (b = 0.09, 90% CIs = 0.001, 0.023) via the neuroimaging phenotype. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.09, 90% CIs = 0.003, 0.022) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.
AB - There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5x10-6 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.06, 90% CIs = 0.001, 0.019) and BMI (b = 0.09, 90% CIs = 0.001, 0.023) via the neuroimaging phenotype. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.09, 90% CIs = 0.003, 0.022) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.
U2 - 10.1038/s41380-019-0444-y
DO - 10.1038/s41380-019-0444-y
M3 - Article
SN - 1359-4184
VL - 0
SP - 1
EP - 10
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 0
ER -