ABSTRACT
Introduction............................................................................................................ 169 11.1 Association Studies: Definitions and Mechanisms ..................................... 170
11.1.1 Case Control Association Study...................................................... 170 11.1.2 Family-Based Association Studies .................................................. 171
11.2 Advantage of Association Studies ............................................................... 172 11.2.1 Power................................................................................................ 172 11.2.2 Linkage Disequilibrium ................................................................... 173
11.3 Limitations of Association Studies.............................................................. 173 11.3.1 False Positives: Linkage Disequilibrium
and Control Groups.......................................................................... 174 11.3.2 Statistical Power: Accept or Reject an Association........................ 175 11.3.3 Consequences in Neurobehavioral Genetics ................................... 175
11.4 Progress in Neurobehavioral Genetics ........................................................ 176 11.4.1 One Gene … Many Phenotypes (the Case
of Phenotypical Heterogeneity) ....................................................... 177 11.4.2 One Phenotype … Many Genes (the Case
of Genetic Heterogeneity)................................................................ 177 11.4.3 Interaction between the Environment and Genetic
Vulnerability..................................................................................... 178 11.5 Conclusions .................................................................................................. 180 References.............................................................................................................. 180
In the beginning of the twenty-first century, the fiftieth anniversary of the discovery of DNA was celebrated, and despite the rapid progress in both human genetics and molecular biological technologies since, neurobehavioral genetics has provided us with only its first promising successes. The human genome has a physical size of 3×109 base pairs that encode and regulate approximately 32,000 genes. Some of
these genes play a role in the aetiology of psychiatric disorders. However, the model of segregation for these disorders does not follow a simple Mendelian trait but follows complex traits where both polygenetic and environmental factors influence the susceptibility to neurobehavioral diseases. The use of association studies to complement linkage analyses provides a powerful tool to identify the genetic component in psychiatric disorders.
