Assessing the statistical power to detect linkage in a sample of 51 bipolar affective disorder pedigrees

Lim, Lionel C. C., Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Sham, Pak, Nothen, Markus M., Korner, Judith, Rietschel, Marcella, Fimmer, Rolf, Propping, Peter, McGuffin, Peter, Murray, Robin and Gill, Michael 1996. Assessing the statistical power to detect linkage in a sample of 51 bipolar affective disorder pedigrees. Behavior Genetics 26 (2) , pp. 113-122. 10.1007/bf02359889

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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 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 theta 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Publisher:	Springer Verlag
ISSN:	0001-8244
Funders:	Wellcome Trust
Last Modified:	27 Oct 2022 08:50
URI:	https://orca.cardiff.ac.uk/id/eprint/63506

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