A linkage tournament: affection status, parametric analysis, multivariate traits, and enhancements to variance components and relative pairs

Linkage tests to localize oligogenes have been extended during the past year. Using simulated data and multiplex selection we find that several tests on affected sib pairs have comparable power and type I error. Three variants of SIBPAL2 are favoured when substantial numbers of normal sibs are included, but performance relative to the BETA benchmark degrades rapidly as normal sibs are depleted by selective sampling or typing. Neglect of this fact may explain recent failure of retrospective collaboration to confirm asthma candidates in the 5q cytokine region that are supported by other studies. A fully quantitative trait favours variance components under complete ascertainment and two options in SIBPAL2 under multiplex selection, with substantial gain in power from covariance analysis if the covariate is independent of the candidate locus. A dichotomy and liability threshold give virtually identical results in the SOLAR variance components program. Comparison with single-marker parametric analysis suggests that extension to multiple markers would be competitive with nonparametric methods in power, and superior in depth of genetic analysis. The simulated examples illustrate common problems encountered with linkage scans for oligogenes. They show that nonparametric methods provide no panacea for analytical problems posed by different phenotypes and methods of ascertainment.