A posterior probability of linkage-based re-analysis of schizophrenia data yields evidence of linkage to chromosomes 1 and 17.
OBJECTIVE
Linkage analysis using 22 Canadian pedigrees identified a promising schizophrenia candidate region on 1q23 with a maximum 2-point HLOD under a recessive model of 5.8 [Brzustowicz et al. 2000]. In the current study, we revisited this data set using a Bayesian linkage analysis technique, namely the posterior probability of linkage (PPL).


METHODS
The PPL has been developed as an alternative to traditional linkage analysis. It differs from both LOD scores and 'non-parametric' methods in that it directly measures the probability of linkage given the data, and incorporates prior genomic information.


RESULTS
As expected, PPL results for 1q23 supported the previously observed linkage, with an estimated multipoint PPL of 99.7%. However, the PPL supported two further results: a second peak on chromosome 1 at 1p13 with a multipoint with PPL of 70% and a chromosome 17 marker (D17S784 at 17q25) with a multipoint PPL of 44%.


CONCLUSIONS
The PPL-based analysis presented has the advantage over other likelihood-based linkage methods in that it avoids maximization and produces a less complex view of the strength of evidence for linkage.
Logue
M W
MW
Program for Public Health Genetics, Center for Statistical Genetics Research, Iowa City, IA 52242, USA. mark-logue@uiowa.edu
Brzustowicz
L M
LM
Bassett
A S
AS
Chow
E W C
EW
Vieland
V J
VJ
D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D008040:Genetic Linkage; D005828:Genetics, Population / Q000706:statistics & numerical data; D006801:Humans; D008126:Lod Score; D015233:Models, Statistical; D011336:Probability; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*