March 2004

The Burden of Complex Genetics in Brain Disorders

Author Affiliations

From the Molecular Neurobiology Branch, National Institute on DrugAbuse Intramural Research Program, National Institutes of Health (Dr Uhl andMr Grow), and the Department of Medicine, The Johns Hopkins University Schoolof Medicine (Mr Grow), Baltimore, Md.


Copyright 2004 American Medical Association. All Rights Reserved.Applicable FARS/DFARS Restrictions Apply to Government Use.2004

Arch Gen Psychiatry. 2004;61(3):223-229. doi:10.1001/archpsyc.61.3.223

Background  Few data estimate the impact of complex genetics in neuropsychiatric illness, making it likely that this impact could be underappreciated.

Objective  To provide estimates of the impact of complex genetics in neuropsychiatric disorders in the United States, based on estimates of disease costs to US society, disease heritability, and mendelian contributions to disease.

Data Sources, Study Selection, and Data Extraction  Costs were estimated from literature sources and Lewin–National Foundation for Brain Research estimates updated for population growth and consumer price index inflation. Heritability estimates came from available twin data. Estimates of mendelian contributions came from the Online Mendelian Inheritance in Man database and our perspectives.

Conclusions  Brain and nervous system disorders may cost the United States as much as $1.2 trillion annually, and affect many millions of Americans each year. Twin data suggest that more than 40% of the societal burden of brain disorders is likely to be genetically mediated. Most of this disease burden arises from complex multigene genetics as well as from environmental influences. The large sizes of these complex genetic burdens should encourage careful molecular and clinical work to link disease-vulnerability allelic variants with the pathogenesis, nosologic characteristics, prevention, diagnostics, and therapeutics of brain disorders.