Improved inference of relationship for pairs of individuals

Am J Hum Genet. 2000 Nov;67(5):1219-31. doi: 10.1016/S0002-9297(07)62952-8. Epub 2000 Oct 13.


Linkage analyses of genetic diseases and quantitative traits generally are performed using family data. These studies assume the relationships between individuals within families are known correctly. Misclassification of relationships can lead to reduced or inappropriately increased evidence for linkage. Boehnke and Cox (1997) presented a likelihood-based method to infer the most likely relationship of a pair of putative sibs. Here, we modify this method to consider all possible pairs of individuals in the sample, to test for additional relationships, to allow explicitly for genotyping error, and to include X-linked data. Using autosomal genome scan data, our method has excellent power to differentiate monozygotic twins, full sibs, parent-offspring pairs, second-degree (2 degrees ) relatives, first cousins, and unrelated pairs but is unable to distinguish accurately among the 2 degrees relationships of half sibs, avuncular pairs, and grandparent-grandchild pairs. Inclusion of X-linked data improves our ability to distinguish certain types of 2 degrees relationships. Our method also models genotyping error successfully, to judge by the recovery of MZ twins and parent-offspring pairs that are otherwise misclassified when error exists. We have included these extensions in the latest version of our computer program RELPAIR and have applied the program to data from the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus (FUSION) study.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Chromosome Mapping / methods*
  • Computer Simulation
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Gene Frequency / genetics
  • Genetic Linkage / genetics
  • Genetic Markers / genetics
  • Genetic Testing
  • Genotype
  • Humans
  • Likelihood Functions
  • Male
  • Matched-Pair Analysis*
  • Models, Genetic
  • Multicenter Studies as Topic
  • Nuclear Family
  • Pedigree
  • Research Design
  • Software
  • Twins, Monozygotic
  • X Chromosome / genetics


  • Genetic Markers