Affected sib-pair interval mapping and exclusion for complex genetic traits: Inferring identity by descent status from relatives
- Univ. of Michigan, Ann Arbor, MI (United States); and others
Affected sib-pair (ASP) methods provide a useful approach for the initial genetic mapping of complex diseases for which mode of inheritance is uncertain. Risch described a method for interval mapping and exclusion based on the ratio lambda comparing disease risk in the first degree relatives of affected individuals to disease risk in the general population. He assumed marker identity by descent (IBD) status for the ASP could be deduced from parental genotypes. For late onset diseases such as type 2 diabetes, parents may be dead or otherwise unavailable, so that marker IBD status generally cannot be inferred with certainty. Guo has developed efficient methods for probabilistic determination of marker IBD sharing for two or more loci. We have combined and extended the methods of Risch and Guo to carry out interval mapping and exclusion when parents are missing but other relatives such as additional siblings are available. Our method is based on calculating the likelihood of marker data of the ASP and their relatives conditional on the disease status of the ASP, as a function of lambda and the position of the disease locus within the genetic map. We currently are using this method to compare the information to detect or exclude linkage provided by various types of ASP nuclear families -- zero, one, or two typed parents and zero, one, two, or more additional siblings -- as a function of sample size, marker density and informativity, and risk ratio lambda.
- OSTI ID:
- 133364
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0092
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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