Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan

Area of Science:

• Behavioral Genetics
• Psychiatric Genetics
• Longevity Research

Background:

• Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with a doubled mortality rate compared to the general population.
• Factors contributing to reduced lifespan in ADHD include lifestyle behaviors, social adversity, and comorbid mental health conditions.

Purpose of the Study:

• To investigate the genetic correlation between ADHD and lifespan using genome-wide association studies (GWAS).
• To identify shared genetic loci and assess the causal relationship between ADHD liability and lifespan.

Main Methods:

• Utilized GWAS data for ADHD and parental lifespan as a proxy for individual lifespan.
• Estimated genetic correlation and identified jointly associated genetic loci.
• Performed Mendelian randomization analyses to assess causality.

Main Results:

• Confirmed a significant negative genetic correlation between ADHD and parental lifespan (rg = -0.36).
• Identified 19 independent loci jointly associated with both ADHD and parental lifespan; alleles increasing ADHD risk were linked to shorter lifespan.
• Mendelian randomization suggested a potential causal effect of ADHD liability on reduced lifespan, though not fully confirmed by all sensitivity analyses.

Conclusions:

• This study provides the first evidence of a common genetic background influencing both ADHD and lifespan.
• The findings support a biological mechanism underlying the increased mortality risk observed in individuals with ADHD.
• Results align with epidemiological data on reduced lifespan in mental disorders, highlighting ADHD as a significant health concern impacting life outcomes.