Genetic Linkage and Association Studies in Bipolar Affective Disorder: A Time for Optimism

Thomas G. Schulze, Francis J. McMahon

Research output: Contribution to journalReview articlepeer-review


Genetic research on complex diseases is beginning to bear fruit, with the successful identification of candidate susceptibility genes in diabetes, asthma, and other illnesses. Similar success is on the horizon for bipolar affective disorder (BPAD), but significant challenges remain. In this review, we outline the basic concepts of linkage and association mapping for complex phenotypes. We point out important caveats inherent in both approaches, and review guidelines on the interpretation of linkage statistics and significance thresholds. We then apply these concepts to an evaluation of the present status of genetic linkage and association studies in BPAD. The challenges posed by locus heterogeneity, phenotype definition, and sample size requirements are given a detailed treatment. Despite these challenges, we argue that the way ahead remains firmly rooted in linkage studies, complemented by association studies in linked regions. This is the only truly genome-wide approach currently available; it has succeeded in other complex phenotypes, and it is the surest strategy for mapping susceptibility genes in BPAD. Once these genes are identified, genetic mapping methods will yield to the other methods of 21st-century molecular biology as we begin to elucidate the pathophysiology of BPAD.

Original languageEnglish (US)
Pages (from-to)36-47
Number of pages12
JournalAmerican Journal of Medical Genetics - Seminars in Medical Genetics
Volume123 C
Issue number1
StatePublished - Nov 15 2003


  • Ascertainment
  • LOD score
  • Linkage disequilibrium
  • Parametric and non-parametric linkage studies
  • Phenotype
  • Sample size

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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