Published Online
on February 22, 2007

A more recent version of this article appeared on April 1, 2007

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Submitted on September 7, 2006
Revised on October 26, 2007
Accepted on November 7, 2006

Model-Based Linkage Analyses Confirm Chromosome 19q13.3 as a Susceptibility Locus for Intracranial Aneurysm

Youhei Mineharu MD; Kayoko Inoue MD, MPH, PhD; Sumiko Inoue PhD; Shigeki Yamada MD, PhD; Kazuhiko Nozaki MD, PhD; Nobuo Hashimoto MD, PhD; and Akio Koizumi MD, PhD^*

From the Departments of Neurosurgery (Y.M., K.N., N.H.) and Health and Environmental Sciences (Y.M., K.I., S.I., A.K.), Kyoto University Graduate School of Medicine, Kyoto, Japan; and the Departments of Neurosurgery and Neurosurgery (S.Y.), Shiga Medical Center for Adults, Shiga, Japan.

^* To whom correspondence should be addressed. E-mail: koizumi{at}pbh.med.kyoto-u.ac.jp.

Background and Purpose--In previous studies of familial intracranial aneurysm (IA), parametric linkage analyses have been undertaken for five unrelated families, four providing maximum logarithm of odds (LOD) scores with dominant models and one with a recessive model. Each family was linked to a distinct locus, indicating locus heterogeneity. This study aimed to examine whether Japanese IA families consistent with autosomal-dominant mode of inheritance support linkage to these loci.

Methods--We performed genomewide linkage analysis using the GENEHUNTER program. Affected-only parametric linkage analysis was used for 41 affected members in nine unrelated IA families with dominant models, which were selected from 29 families used for a nonparametric (model-free) linkage analysis in our previous study.

Results--We failed to support the linkage to previously reported autosomal-dominant loci. Instead, we found linkage to chromosome 19q13.3 with a maximum multipoint LOD score of 4.10. The LOD-1 interval (regions with LOD scores of >1) was 8.0 cM between D19S198 and D19S902.

Conclusions--A genomewide scan for IA families with dominant models in Japan confirmed the locus at chromosome 19q13.3, which has also been reported as a candidate locus in a Finnish population.

Key words: autosomal-dominant • familial • genetics • intracranial aneurysm • linkage

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