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Identification of a Major Gene Locus

Elizabeth Dorus, PhD; Nancy J. Cox, PhD; Robert D. Gibbons, PhD; Rita Shaughnessy, PhD; Ghanshyam N. Pandey, PhD; C. Robert Cloninger, MD

Arch Gen Psychiatry. 1983;40(5):545-552.

Abstract
• We have identified a genetic polymorphism in which one allele results in elevated RBC lithium ion ratios and also contributes to vulnerability to some forms of affective disorders. Interindividual variability in the lithium ion ratio (the ratio of the RBC to the plasma lithium ion concentration) is determined by variability in a lithium-sodium ion counterflow mechanism. Segregation analyses were conducted on lithium ion ratios in vitro in members of 120 normal families and on both the lithium ion ratio and the history of affective disorder in first-degree relatives of 31 bipolar patients. These analyses provided evidence for an autosomal major gene locus that influences the lithium ion ratio both in members of normal families and in relatives of bipolar patients. The allele at the major locus resulting in elevated lithium ion ratios was associated with an increased likelihood of psychiatric hospitalization among relatives of bipolar patients.

Author Affiliations
From the Department of Psychiatry, University of Chicago (Drs Dorus and Shaughnessy), the Departments of Psychiatry (Drs Cox and Cloninger) and Genetics (Dr Cloninger), Washington University, St Louis, and the Department of Psychiatry, University of Illinois at the Medical Center, Chicago (Drs Gibbons and Pandey).

Footnotes
Accepted for publication Nov 29, 1982.

Reprint requests to Department of Psychiatry, University of Chicago, 950 E 59th St, Chicago, IL 60637 (Dr Dorus).

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