학술논문

Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan
Document Type
article
Source
Neuropsychopharmacology. 48(7)
Subject
Biological Psychology
Psychology
Genetics
Mental Illness
Prevention
Human Genome
Attention Deficit Hyperactivity Disorder (ADHD)
Mental Health
Brain Disorders
Aging
Behavioral and Social Science
Pediatric
2.1 Biological and endogenous factors
2.3 Psychological
social and economic factors
Mental health
Good Health and Well Being
Humans
Attention Deficit Disorder with Hyperactivity
Genome-Wide Association Study
Longevity
Phenotype
Mendelian Randomization Analysis
Medical and Health Sciences
Psychology and Cognitive Sciences
Psychiatry
Neurosciences
Biological psychology
Language
Abstract
There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = -0.36, P = 1.41e-16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e-06; Beta = -0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes.