Posterior probability of linkage analysis of autism dataset identifies linkage to chromosome 16.
OBJECTIVE
To apply phenotypic and statistical methods designed to account for heterogeneity to linkage analyses of the autism Collaborative Linkage Study of Autism (CLSA) affected sibling pair families.


METHODS
The CLSA contains two sets of 57 families each; Set 1 has been analyzed previously, whereas this study presents the first analyses of Set 2. The two sets were analyzed independently, and were further split based on the degree of phrase speech delay in the siblings. Linkage analysis was carried out using the posterior probability of linkage (PPL), a Bayesian statistic that provides a mathematically rigorous mechanism for combining linkage evidence across multiple samples.


RESULTS
Two-point PPLs from Set 1 led to the follow-up genotyping of 18 markers around linkage peaks on 1q, 13p, 13q, 16q, and 17q in both sets of families. Multipoint PPLs were then calculated for the entire CLSA sample. These analyses identified four regions with at least modest evidence in support of linkage: 1q at 173 cM, PPL=0.12; 13p at 21 cM, PPL=0.16; 16q at 63 cM, PPL=0.36; Xq at 40 cM, PPL=0.11.


CONCLUSIONS
We find strengthened evidence for linkage of autism to chromosomes 1q, 13p, 16q, and Xq, and diminished evidence for linkage to 7q and 13q. The verity of these findings will be tested by continuing to update our PPL analyses with data from additional autism datasets.
Wassink
Thomas H
TH
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. thomas-wassink@uiowa.edu
Vieland
Veronica J
VJ
Sheffield
Val C
VC
Bartlett
Christopher W
CW
Goedken
Rhinda
R
Childress
Deborah
D
Piven
Joseph
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001321:Autistic Disorder / Q000453:epidemiology / Q000235:genetics*; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D002877:Chromosomes, Human / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D035781:Siblings / Q000523:psychology; D014481:United States / Q000453:epidemiology
D005819:Genetic Markers