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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e120.)
© 2006 American Heart Association, Inc.

Letters to the Editor

Longitudinal Differences in Familial Combined Hyperlipidemia Quantitative Trait Loci

Rebecca L. Pollex

Robarts Research Institute, London, Ontario, Canada

Robert A. Hegele

Robarts Research Institute and Department of Medicine and Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In response:

Previously in Arteriosclerosis, Thrombosis, and Vascular Biology we commented on genome-wide linkage analysis of quantitative trait loci (QTL) as a strategy to solve the genetics of complex traits, such as familial combined hyperlipidemia (FCHL).¹ We noted that although this approach has yielded numerous linkage peaks, only rarely have these peaks led to defined molecular genetic determinants.¹ We suggested that replication of QTL analysis is an important filtering process to increase confidence in preliminary observations by reducing false-positive leads.¹ The usual replication strategy involves repeating the analysis in independent samples and identifying shared peaks. In their letter, Brouwers et al report the use of an alternate replication strategy, namely repeating QTL analysis for FCHL in the same cohort after an elapsed time period of 5 years.² On first glance, this strategy would appear quite likely to yield replicable results, considering that the same subjects should be stable for both their genotype (definitely) and for their quantitative phenotypes (essentially) over time.

In the baseline study performed using phenotypes collected in 1999,³ Cantor et al identified 4 peaks, using the threshold of P<0.001 to report significant linkage. These peaks were located at chromosome 1p21-31 and 17p11-q23 for apoB, 12p13 for cholesterol, and 4p15-16 for triglycerides. Each QTL was re-examined in their follow-up study of the same subjects using phenotypes collected in 2004.² First, the unambiguous good news: the peak at 1p21-31 for apoB was replicated, with virtually the same contour and significance observed for the follow-up analysis compared with baseline. . . . [Full Text of this Article]

This article has been cited by other articles:

				M. C. G. J. Brouwers, R. M. Cantor, N. Kono, J. l. Yoon, C. J. H. van der Kallen, M. A. L. Bilderbeek-Beckers, M. M. J. van Greevenbroek, A. J. Lusis, and T. W. A. de Bruin Heritability and genetic loci of fatty liver in familial combined hyperlipidemia J. Lipid Res., December 1, 2006; 47(12): 2799 - 2807. [Abstract] [Full Text] [PDF]