A simulated genetic structure for bipolar illness

✍ Scribed by John I. Nurnberger Jr.

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 236 KB
• Volume: 147B
• Category: Article
• ISSN: 1552-4841
• DOI: 10.1002/ajmg.b.30724

✦ Synopsis

Abstract

Bipolar illness is conceptualized as a polygenic condition. Based on candidate gene findings from the literature to date, up to 22% of the genetic risk in affected persons may be explained by six gene variants with an average allele frequency of 0.59 in cases and 0.54 in controls. The mean allele specific relative risk (ASRR) for these variants is 1.42 (range 1.1–1.8). Initial results from genome‐wide association studies tend to confirm this estimate of effect size. Using the characteristics of these variants as a guide, a 30 allele model for bipolar illness is presented in which the modal affected person would carry 22 susceptibility variants, and the median unaffected person would carry 15. In a comparable model with 100 alleles, the modal affected person would carry 62 susceptibility variants compared with a median of 50 in unaffecteds. To the extent that common gene variants are associated with bipolar disorder they may be expected to also be widely distributed in the general population. As the neurobiology of replicated candidate genes is considered, models of potentially relevant biological pathways may be constructed. © 2008 Wiley‐Liss, Inc.