Linkage of chromosome 1 markers to alcoholism-related phenotypes by sib pair linkage analysis of principal components

Using the Collaborative Study on the Genetics of Alcoholism data and affect ed-sib-pair linkage methods, Reich et al. [1998] reported linkage of alcoho l dependence to a region near D1S1588 on chromosome I. In this paper, we as sessed the ability of multivariate sib-pair linkage analysis of the neuroph ysiologic measurements (including age and sex) to evaluate evidence for lin kage to chromosome 1. Principal components of 16 neurophysiologic measureme nts, plus age and sex, were analyzed separately using sib-pair linkage anal ysis, and a cumulative sum of the resulting t(2)-statistics computed at eac h point on the chromosome. The first four principal components, which accou nted for 74% of the total variation, showed little or no evidence for linka ge in the D1S1588 region, while the remaining components showed substantial evidence for linkage. We conclude that potentially important linkage resul ts can be missed if investigators limit attention only to major sources of variability. (C) 1999 Wiley-Liss, Inc.