The initial approach was to use linkage studies in extended and densely affected pedigrees, 11 , 15 , 16 where the key question was whether large sections of chromosomes (measured in centiMorgans, approximately 1 Mb) co‐segregated with AUD within families at a level greater than expected by chance (i.e., observed vs. expected identity‐by‐descent). These linkage studies were influential at the time, identifying regions on chromosome 4q23 that harbored the alcohol dehydrogenase genes (e.g., ADH1B), as well as a cluster of genes on 4p12 encoding Gamma‐aminobutyric acid receptor genes linked to a quantitative EEG phenotype and AUD. 17 , 18 , 19 The extensive phenotyping of the sample also facilitated the study of quantitative traits, such as maximum drinks in a 24 h period 20 and substance dependence symptom counts, 21 which are presumed to provide greater power and precision, 22 especially with multi‐point extensions (i.e., leveraging identity‐by‐descent among many different types of relative pairs in pedigrees of arbitrary size). 23 COGA linkage data were also pivotal in advancing methods for linkage analysis as part of two Genetic Analysis Workshops (e.g., Genetic Analysis Workshop 11, 24 Genetic Analysis Workshop 14 25 ).
