The Current Status of Genetic Linkage Studies of Alcoholism and Unipolar Depression

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Abstract
One of the long term goals of psychiatric research has been to identify distinct homogeneous disease entities not only from a clinical standpoint, but also from a biological, or genetic, standpoint as well. The identification of homogeneous disease entities can be facilitated with the use of genetic linkage analysis. Here we review twelve studies that present results of sib-pair and lod score linkage analyses of alcoholism and/or subclassifications of unipolar depression, and pool their results. The results reviewed here are striking in one respect. Of the ten studies that used a sib-pair method of analysis, six suggested evidence of linkage between the various unipolar affective disorders and markers in two linkage groups—the MNS–GC linkage group on chromosome 4q and the ABO-AK1-ORM linkage group on chromosome 9q. A seventh study had nominal significance levels of 0.06 and 0.07 with the GC and MNS loci, respectively. Of the eight studies that used lod score linkage analysis, four also suggested evidence of linkage (nominal p ≤ 0.05) with markers in either of these two linkage groups. Possible evidence of linkage or association to markers in either of these two linkage groups was found in seven of the nine independent sets of families involved.

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