Multifactorial Analysis of Family Data Ascertained Through Truncation: a Comparative Evaluation of Two Methods of Statistical Inference
Overview
Affiliations
When family data are ascertained through single selection based on truncation, a prevailing method of analysis is to condition the likelihood function on the proband's actual phenotypic value. An alternative method conditions the likelihood function on the event that the proband's measurement lies in the truncation region. Both methods are contrasted here by using Monte Carlo simulations; identical sets of data were analyzed using both methods. The results suggest that, under either method, (1) parameter estimates are nearly unbiased and (2) likelihood-ratio tests of null hypotheses are approximately distributed as chi 2. However, conditioning on the proband's actual phenotypic value yields considerably less efficient estimates and reduced power for hypothesis tests. A corresponding result also holds under complete ascertainment. It is argued, therefore, that whenever sufficient information is available on the nature of truncation, the alternative approach should be used.
Identification of genetic loci underlying the phenotypic constructs of autism spectrum disorders.
Liu X, Georgiades S, Duku E, Thompson A, Devlin B, Cook E J Am Acad Child Adolesc Psychiatry. 2011; 50(7):687-696.e13.
PMID: 21703496 PMC: 3593812. DOI: 10.1016/j.jaac.2011.05.002.
A framework for structural equation models in general pedigrees.
Morris N, Elston R, Stein C Hum Hered. 2011; 70(4):278-86.
PMID: 21212683 PMC: 3164176. DOI: 10.1159/000322885.
Genome-wide linkage analyses of quantitative and categorical autism subphenotypes.
Liu X, Paterson A, Szatmari P Biol Psychiatry. 2008; 64(7):561-70.
PMID: 18632090 PMC: 2670970. DOI: 10.1016/j.biopsych.2008.05.023.
Large upward bias in estimation of locus-specific effects from genomewide scans.
Goring H, Terwilliger J, Blangero J Am J Hum Genet. 2001; 69(6):1357-69.
PMID: 11593451 PMC: 1235546. DOI: 10.1086/324471.
Correcting for single ascertainment by truncation for a quantitative trait.
Young M, Boehnke M, Moll P Am J Hum Genet. 1988; 43(5):705-8.
PMID: 3189333 PMC: 1715533.