The genetics of adult-onset neuropsychiatric disease: complexities and conundra?

Science. 2003 Oct 31;302(5646):822-6. doi: 10.1126/science.1092132.


Genetic factors play a major role in the etiology of adult-onset neurodegenerative and neuropsychiatric disorders. Several highly penetrant genes have been cloned for rare, autosomal-dominant, early-onset forms of neurodegenerative diseases. These genes have provided important insights into the mechanisms of these diseases (often altering neuronal protein processing). However, the genes associated with inherited susceptibility to late-onset neurodegenerative diseases, schizophrenia, and bipolar disorder appear to have smaller effects and are likely to interact with each other (and with nongenetic factors) to modulate susceptibility and/or disease phenotype. Several strategies have recently been applied to address this complexity, leading to the identification of a number of candidate susceptibility loci/genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adult
  • Alzheimer Disease / genetics
  • Bipolar Disorder / genetics
  • Chromosome Mapping
  • Dementia / genetics
  • Genetic Heterogeneity
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Humans
  • Mental Disorders / genetics*
  • Middle Aged
  • Multifactorial Inheritance*
  • Neuregulin-1 / genetics
  • Neurodegenerative Diseases / genetics*
  • Phenotype
  • Schizophrenia / genetics


  • Neuregulin-1