Assessing the statistical power to detect linkage in a sample of 51 bipolar affective disorder pedigrees |
| |
Authors: | Lionel C C Lim Nick Craddock Mike Owen Pak Sham Markus M Nöthen Judith Körner Marcella Rietschel Rolf Fimmer Peter Propping Peter McGuffin Robin Murray Michael Gill |
| |
Institution: | (1) Genetics Section, Institute of Psychiatry, De Crespigny Park, SE5 8AF London, England;(2) Department Psychological Medicine, University of Wales College of Medicine, CX4 4XN Cardiff, Wales;(3) Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, D-5300 Bonn 1, Germany;(4) Department of Psychiatry, University of Bonn, Bonn, Germany;(5) Institute for Medical Statistics, University of Bonn, Bonn, Germany;(6) Department of Psychological Medicine, National University of Singapore, 0511 Singapore, Republic of Singapore;(7) Department of Psychological Medicine, National University Hospital, 0511 Singapore, Republic of Singapore |
| |
Abstract: | We used computer simulation method to address the question of power in an initial collaborative sample of 51 bipolar affective
disorder pedigrees. Simulations were performed for all possible combinations using (1) two levels of diagnostic stringency,
(2) three transmission models, (3) locus heterogeneity, and (4) different assumed phenocopy rates. Some of the factors that
affect the power to detect linkage are (1) the specification of the correct genetic model, (2) the degree of locus heterogeneity,
and (3) the frequency of phenocopies. The first two assertions were supported by our simulation results, but varying the rates
of phenocopy did not substantially alter the power of the sample until a critical point. However, it is important to point
out that these results are dependent on the genetic models under study and on the use of the “correct” model (i.e., the one
used to simulate the data). If we assume a dominant mode of inheritance and locus homogeneity, the power to detect linkage
is 97.5% at a θ of .01. However, the power declines dramatically, to 60.5 and 14.7%, if only 75 and 50% of the families are
linked, respectively. Locus heterogeneity has a similar effect on the power of the sample to exclude linkage. The relative
lack of power in our data, in the presence of significant locus heterogeneity, and for an intermediate mode of inheritance,
underscores the need for multicenter collaboration. |
| |
Keywords: | Computer simulation locus heterogeneity phenocopies linkage analysis |
本文献已被 SpringerLink 等数据库收录! |
|