Three potential susceptibility loci shown by a genome-wide scan for regions influencing the age at onset of mania.
OBJECTIVE
The age at onset of bipolar disorder is associated with clinical features of the illness, including duration, severity, and pattern of comorbidity with other disorders. Age at onset is familial and heritable, and it correlates inversely with the prevalence of bipolar disorder among relatives. Because age at onset may have utility in resolving the complexity and heterogeneity of the disorder, the authors sought to identify chromosomal loci that harbor the genes influencing this trait.


METHODS
A genome scan of 539 genotyped people in 97 families ascertained for the NIMH Bipolar Disorder Genetics Initiative was performed by using multipoint variance-components linkage analysis.


RESULTS
The age at onset of mania was significantly heritable in these families. Three chromosomal regions yielded nonsignificant but suggestive multipoint lod scores greater than 2.5, with the strongest evidence observed at markers D12S1292, GATA31B, and GATA50C, on chromosomes 12p, 14q, and 15q, respectively.


CONCLUSIONS
Although firm conclusions await an independent replication, these results suggest that three regions of the genome may contain genes influencing the age at onset of mania in bipolar disorder. To the authors' knowledge, these regions have not been implicated previously in risk for the disorder, suggesting that separate sets of genes influence disease susceptibility and the age at which it appears.
Faraone
Stephen V
SV
Department of Psychiatry, Harvard Medical School, Boston, USA. sfaraone@hms.harvard.edu
Glatt
Stephen J
SJ
Su
Jessica
J
Tsuang
Ming T
MT
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D017354:Point Mutation / Q000235:genetics*
D005819:Genetic Markers