A simulated genetic structure for bipolar illness.
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.
Nurnberger
John I
JI
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, 791 Union Drive, IUMC/IPR, Indianapolis, IN 46202-4887, USA. jnurnber@iupui.edu
D001714:Bipolar Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D003198:Computer Simulation; D005787:Gene Frequency; D008040:Genetic Linkage / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008957:Models, Genetic; D008995:Monoamine Oxidase / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D014481:United States
D002352:Carrier Proteins; C475071:DAOA protein, human; C412476:DISC1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C548226:P2RX4 protein, human; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D050486:Serotonin Plasma Membrane Transport Proteins; D008995:Monoamine Oxidase