Premium
Genetic linkage and association studies in bipolar affective disorder: A time for optimism
Author(s) -
Schulze Thomas G.,
McMahon Francis J.
Publication year - 2003
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.20012
Subject(s) - genetic association , linkage (software) , genetic linkage , genome wide association study , candidate gene , genetics , genetic heterogeneity , biology , locus (genetics) , identification (biology) , computational biology , bipolar disorder , phenotype , evolutionary biology , gene , single nucleotide polymorphism , genotype , neuroscience , cognition , botany
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. © 2003 Wiley‐Liss, Inc.