Independent replication and initial fine mapping of 3p21-24 in Asperger syndrome.

BACKGROUND: Asperger syndrome is characterised by abnormalities in social interaction as well as repetitive and stereotyped behaviours and interests. The trait is thought to display complex inheritance, but in a subset of families the inheritance resembles the autosomal dominant model. Linkage to 3p14-24 has recently been reported in Asperger syndrome in Finnish families with a maximum multipoint NPL(all) of 3.32 at D3S2432. METHODS: We have replicated linkage findings to 3p21-24 in 12 new extended Asperger syndrome families. Linkage analyses were performed separately for the 12 new families, and linkage and association analyses were also performed jointly with data from the original genome-wide screen. RESULTS: Best two point and multipoint logarithm of the odds (LOD) scores in analyses of both data sets were obtained at D3S2432 (NPL(all) = 3.83) with both subsets of families contributing to linkage. Association analysis of the combined data set produced a trend towards association with D3S2432 and D3S1619. CONCLUSIONS: This study further validates 3q21-24 as a candidate region for Asperger syndrome.

Genome-wide scan for loci of Asperger syndrome.

Asperger syndrome (AS), characterised by inadequate social interaction, lack of empathy and a dependence of routines and rituals, is classified as belonging to the autism spectrum disorders (DSM-IV and ICD-10). Although the prevalence of AS has been estimated to range from 0.3 up to 48.4 per 10 000, the phenotype still remains relatively unrecognised by clinicians. Several reports, including the original description by Hans Asperger (1944), have suggested that AS has a strong genetic component. Here, we have performed a genome-wide scan on Finnish families ascertained for AS with a strictly defined phenotype. In the initial scan, Z(max)>1.5 was observed on nine chromosomal regions, 1q21-22, 3p14-24, 3q25-27, 4p14, 4q32, 6p25, 6q16, 13q31-33 and 18p11. In the fine mapping stage, the highest two-point LOD scores were observed on chromosomes 1q21-22 (D1S484, Z(max dom)=3.58), 3p14-24 (D3S2432, Z(max dom)=2.50) and 13q31-33 (D13S793, Z(max dom)=1.59). The loci on 1q21-22 and 3p14-24 overlap with previously published autism susceptibility loci, and the loci on 1q21-22 and 13q31-33 overlap with the reported schizophrenia susceptibility loci. The present study is the first genome-wide screen in AS and therefore replication data sets are needed to evaluate further the significance of the AS-loci identified here.