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Replication of linkage with bipolar disorder on chromosome 16p in the eastern Quebec population
Author(s) -
Mérette Chantal,
Roy MarcAndré,
Bureau Alexandre,
Fournier Alain,
Émond Claudia,
Cliche Denis,
Jomphe Valérie,
Chag Yvon C.,
Maziade Michel
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30673
Subject(s) - linkage (software) , sample (material) , replication (statistics) , nonparametric statistics , population , sample size determination , lod score , genetics , statistics , psychology , biology , chromosome , medicine , mathematics , chemistry , gene , gene mapping , environmental health , chromatography
In a previous study [Maziade et al. (2005); Mol Psychiatry 10:486–499], we provided evidence for linkage (parametric lod score of 4.05) on chromosome 16p for bipolar affective disorder (BP) in 21 kindreds from Eastern Quebec, a population characterized by a founder effect. Using a stringent design, we performed a replication study in a second sample of 27 kindreds (sample 2) collected from the same population and assessed with the same methodologies as in our original sample (sample 1), that is with the same diagnostic procedure and using a common set of 23 markers studied with model‐based (parametric) and model‐free (nonparametric) linkage analyses. We replicated our initial finding with P values <0.001. Indeed, maximum NPL all scores of 3.7 and 3.52 were found at marker D16S3060 in sample 2 for the narrow and broad BP phenotype definition, respectively. For the latter definition, the nonparametric score reached 3.87 in the combined sample, a value that exceeded the maximum NPL score obtained in each individual sample (NPL all = 2.32 in sample 1; NPL all = 3.52 in sample 2). Moreover, a refined phenotype restricted to BP associated with psychosis yielded significant evidence for linkage in each individual sample (NPL all = 2.38 in sample 1; NPL all = 2.72) while yielding the best result (NPL all score = 3.90) in the combined sample (samples 1 and 2), despite an important reduction in the number of affected individuals. It is also noteworthy that the use of the refined phenotype provided a location of the maximum linkage peak shared by both samples, that is, at marker D16S668 in 16p13.12, suggesting consistency across samples. Our study provided one of the strongest pieces of evidence for linkage with BP in 16p and illustrated the heuristic potential of a replication study in a second sample ascertained from the same population and using homogeneous methodologies. © 2007 Wiley‐Liss, Inc.