Abstract
ObjectiveTwin studies and genome-wide complex trait analysis (GCTA) are not in agreement regarding heritability estimates for behavioral traits in children from the general population. This has sparked a debate on the possible difference in genetic architecture between behavioral traits and psychiatric disorders. In this study, we test whether polygenic risk scores associated with variation in attention-deficit/hyperactivity disorder (ADHD) trait levels in children from the general population predict ADHD diagnostic status and severity in an independent clinical sample.MethodSingle nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of ADHD traits in 4,546 children (mean age, 7 years 7 months) from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis (independent clinical sample) and 5,081 control participants. Polygenic scores were tested for association with case-control status and severity of disorder in the clinical sample.ResultsIncreased polygenic score for ADHD traits predicted ADHD case-control status (odds ratio = 1.17 [95% CI = 1.08–1.28], p = .0003), higher ADHD symptom severity (β = 0.29 [95% CI = 0.04–0.54], p = 0.02), and symptom domain severity in the clinical sample.ConclusionThis study highlights the relevance of additive genetic variance in ADHD, and provides evidence that shared genetic factors contribute to both behavioral traits in the general population and psychiatric disorders at least in the case of ADHD.
Highlights
Single nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of attention-deficit/hyperactivity disorder (ADHD) traits in 4,546 children from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis and 5,081 control participants
This study highlights the relevance of additive genetic variance in ADHD, and provides evidence that shared genetic factors contribute to both behavioral traits in the general population and psychiatric disorders at least in the case of ADHD
T raditional behavioral genetic studies have shown that psychiatric disorders, whether defined categorically as diagnoses or viewed as trait measures, are moderately to highly heritable.[1]. Findings from these family, twin, and adoption studies suggest that many childhood psychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD),[2,3] autism,[4] and depression[5] can be viewed as extremes of dimensional attributes present in the general population
Summary
Single nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of ADHD traits in 4,546 children (mean age, 7 years 7 months) from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis (independent clinical sample) and 5,081 control participants. The polygenic risk score method described by the International Schizophrenia Consortium (ISC) was used in this analysis.[15] A discovery quantitative GWAS of ADHD traits in the Avon Longitudinal Study of Parents and Children (ALSPAC) was used to identify risk alleles associated with higher levels of ADHD traits. ALSPAC, which was used as the discovery sample for this study, is a prospective birth cohort that recruited pregnant women with expected delivery dates between April 1991 and December 1992 from Bristol, United Kingdom. Ethical approval was obtained from the ALSPAC Law and Ethics Committee and the local ethics committees
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