Predicting ADHD in alcohol dependence using polygenic risk scores for ADHD

TY - JOUR

T1 - Predicting ADHD in alcohol dependence using polygenic risk scores for ADHD

AU - Patel, Kejal H.S.

AU - Walters, G. Bragi

AU - Stefánsson, Hreinn

AU - Stefánsson, Kári

AU - Degenhardt, Franziska

AU - Nothen, Markus

AU - Van Der Veen, Tracey

AU - Demontis, Ditte

AU - Borglum, Anders

AU - Kristiansen, Mark

AU - Bass, Nicholas J.

AU - McQuillin, Andrew

N1 - Publisher Copyright: © 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.

PY - 2024/6

Y1 - 2024/6

N2 - Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a high degree of comorbidity, including substance misuse. We aimed to assess whether ADHD polygenic risk scores (PRS) could predict ADHD diagnosis in alcohol dependence (AD). ADHD PRS were generated for 1223 AD subjects with ADHD diagnosis information and 1818 healthy controls. ADHD PRS distributions were compared to evaluate the differences between healthy controls and AD cases with and without ADHD. We found increased ADHD PRS means in the AD cohort with ADHD (mean 0.30, standard deviation (SD) 0.92; p = 3.9 × 10−6); and without ADHD (mean − 0.00, SD 1.00; p = 5.2 × 10−5) compared to the healthy control subjects (mean − 0.17, SD 0.99). The ADHD PRS means differed within the AD group with a higher ADHD PRS mean in those with ADHD, odds ratio (OR) 1.34, confidence interval (CI) 1.10 to 1.65; p = 0.002. This study showed a positive relationship between ADHD PRS and risk of ADHD in individuals with co-occurring AD indicating that ADHD PRS may have utility in identifying individuals that are at a higher or lower risk of ADHD. Further larger studies need to be conducted to confirm the reliability of the results before ADHD PRS can be considered as a robust biomarker for diagnosis.

AB - Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a high degree of comorbidity, including substance misuse. We aimed to assess whether ADHD polygenic risk scores (PRS) could predict ADHD diagnosis in alcohol dependence (AD). ADHD PRS were generated for 1223 AD subjects with ADHD diagnosis information and 1818 healthy controls. ADHD PRS distributions were compared to evaluate the differences between healthy controls and AD cases with and without ADHD. We found increased ADHD PRS means in the AD cohort with ADHD (mean 0.30, standard deviation (SD) 0.92; p = 3.9 × 10−6); and without ADHD (mean − 0.00, SD 1.00; p = 5.2 × 10−5) compared to the healthy control subjects (mean − 0.17, SD 0.99). The ADHD PRS means differed within the AD group with a higher ADHD PRS mean in those with ADHD, odds ratio (OR) 1.34, confidence interval (CI) 1.10 to 1.65; p = 0.002. This study showed a positive relationship between ADHD PRS and risk of ADHD in individuals with co-occurring AD indicating that ADHD PRS may have utility in identifying individuals that are at a higher or lower risk of ADHD. Further larger studies need to be conducted to confirm the reliability of the results before ADHD PRS can be considered as a robust biomarker for diagnosis.

KW - ADHD

KW - alcohol dependence

KW - co-morbidity

KW - co-occurring disorders

KW - polygenic risk scores

KW - Genetic Predisposition to Disease

KW - Comorbidity

KW - Humans

KW - Risk Factors

KW - Middle Aged

KW - Male

KW - Multifactorial Inheritance/genetics

KW - Case-Control Studies

KW - Attention Deficit Disorder with Hyperactivity/genetics

KW - Female

KW - Adult

KW - Genetic Risk Score

KW - Alcoholism/genetics

U2 - 10.1002/ajmg.b.32967

DO - 10.1002/ajmg.b.32967

M3 - Journal article

C2 - 37946686

AN - SCOPUS:85176572176

SN - 1552-4841

VL - 195

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

IS - 4

M1 - e32967

ER -