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Relative risks and effective number of meioses: A unified approach for general genetic models and phenotypes

Kurbasic, Azra LU and Hossjer, O (2006) In Annals of Human Genetics 70(6). p.907-922
Abstract
Many common diseases are known to have genetic components, but since they are non-Mendelian, i.e. a large number of genetic factors affect the phenotype, these components are difficult to localize. These traits are often called complex and analysis of siblings is a valuable tool for mapping them. It has been shown that the power of the affected relative pairs method to detect linkage of a disease susceptibility locus depends on the locus contribution to increased risk of relatives compared with population prevalence Risch, 1990a,b). In this paper we generalize calculation of relative risk to arbitrary phenotypes and genetic models, but also show that the relative risk can be split into the relative risk at the main locus and the relative... (More)
Many common diseases are known to have genetic components, but since they are non-Mendelian, i.e. a large number of genetic factors affect the phenotype, these components are difficult to localize. These traits are often called complex and analysis of siblings is a valuable tool for mapping them. It has been shown that the power of the affected relative pairs method to detect linkage of a disease susceptibility locus depends on the locus contribution to increased risk of relatives compared with population prevalence Risch, 1990a,b). In this paper we generalize calculation of relative risk to arbitrary phenotypes and genetic models, but also show that the relative risk can be split into the relative risk at the main locus and the relative risk due to interaction between the main locus and loci at other chromosomes. We demonstrate how the main locus contribution to the relative risk is related to probabilities of allele sharing identical by descent at the main locus, as well as power to detect linkage. To this end we use the effective number of meioses, introduced by Hossjer (2005a) as a convenient tool. Relative risks and effective number of meioses are computed for several genetic models with binary or quantitative phenotypes, with or without polygenic effects. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
linkage analysis, complex diseases, relative risk, effective number of, meioses
in
Annals of Human Genetics
volume
70
issue
6
pages
907 - 922
publisher
Wiley-Blackwell
external identifiers
  • wos:000241191400022
  • scopus:33749565524
ISSN
1469-1809
DOI
10.1111/j.1469-1809.2006.00266.x
language
English
LU publication?
yes
id
b0aff250-3049-46c8-b39b-0e84b12c5308 (old id 388256)
date added to LUP
2007-10-08 09:33:22
date last changed
2019-02-20 04:27:54
@article{b0aff250-3049-46c8-b39b-0e84b12c5308,
  abstract     = {Many common diseases are known to have genetic components, but since they are non-Mendelian, i.e. a large number of genetic factors affect the phenotype, these components are difficult to localize. These traits are often called complex and analysis of siblings is a valuable tool for mapping them. It has been shown that the power of the affected relative pairs method to detect linkage of a disease susceptibility locus depends on the locus contribution to increased risk of relatives compared with population prevalence Risch, 1990a,b). In this paper we generalize calculation of relative risk to arbitrary phenotypes and genetic models, but also show that the relative risk can be split into the relative risk at the main locus and the relative risk due to interaction between the main locus and loci at other chromosomes. We demonstrate how the main locus contribution to the relative risk is related to probabilities of allele sharing identical by descent at the main locus, as well as power to detect linkage. To this end we use the effective number of meioses, introduced by Hossjer (2005a) as a convenient tool. Relative risks and effective number of meioses are computed for several genetic models with binary or quantitative phenotypes, with or without polygenic effects.},
  author       = {Kurbasic, Azra and Hossjer, O},
  issn         = {1469-1809},
  keyword      = {linkage analysis,complex diseases,relative risk,effective number of,meioses},
  language     = {eng},
  number       = {6},
  pages        = {907--922},
  publisher    = {Wiley-Blackwell},
  series       = {Annals of Human Genetics},
  title        = {Relative risks and effective number of meioses: A unified approach for general genetic models and phenotypes},
  url          = {http://dx.doi.org/10.1111/j.1469-1809.2006.00266.x},
  volume       = {70},
  year         = {2006},
}