Abstract
In a small chromosomal region, a number of polymorphisms may be both linked to and associated with a disease. Distinguishing the potential causal sites from those indirectly associated due to linkage disequilibrium (LD) with a causal site is an important problem. This problem may be approached by determining which of the associations can explain the observed linkage signal. Recently, several methods have been proposed to aid in the identification of disease associated polymorphisms that may explain an observed linkage signal, using genotype data from affected sib pairs (ASPs) [Li et al. [2005] Am. J. Hum. Genet. 76:934-949; Sun et al. [2002] Am. J. Hum. Genet. 70:399-411]. These methods can be used to test the null hypothesis that a candidate single nucleotide polymorphism (SNP) is the sole causal variant in the region, or is in complete LD with the sole causal variant in the region. We extend variations of these methods to test for complete LD between a disease locus and haplotypes composed of two or more tightly linked candidate SNPs. We study properties of the proposed methods by simulation and apply them to type 1 diabetes data for ASPs and their parents at candidate SNP and microsatellite marker loci in the Insulin (INS) gene region.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 727-740 |
| Number of pages | 14 |
| Journal | Genetic Epidemiology |
| Volume | 31 |
| Issue number | 7 |
| DOIs | |
| State | Published - Nov 2007 |
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Keywords
- Association
- Conditional tests
- Fine mapping
ASJC Scopus subject areas
- Genetics(clinical)
- Epidemiology
Cite this
Exploring causality via identification of SNPs or haplotypes responsible for a linkage signal. / Biernacka, Joanna M; Cordell, Heather J.
In: Genetic Epidemiology, Vol. 31, No. 7, 11.2007, p. 727-740.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Exploring causality via identification of SNPs or haplotypes responsible for a linkage signal
AU - Biernacka, Joanna M
AU - Cordell, Heather J.
PY - 2007/11
Y1 - 2007/11
N2 - In a small chromosomal region, a number of polymorphisms may be both linked to and associated with a disease. Distinguishing the potential causal sites from those indirectly associated due to linkage disequilibrium (LD) with a causal site is an important problem. This problem may be approached by determining which of the associations can explain the observed linkage signal. Recently, several methods have been proposed to aid in the identification of disease associated polymorphisms that may explain an observed linkage signal, using genotype data from affected sib pairs (ASPs) [Li et al. [2005] Am. J. Hum. Genet. 76:934-949; Sun et al. [2002] Am. J. Hum. Genet. 70:399-411]. These methods can be used to test the null hypothesis that a candidate single nucleotide polymorphism (SNP) is the sole causal variant in the region, or is in complete LD with the sole causal variant in the region. We extend variations of these methods to test for complete LD between a disease locus and haplotypes composed of two or more tightly linked candidate SNPs. We study properties of the proposed methods by simulation and apply them to type 1 diabetes data for ASPs and their parents at candidate SNP and microsatellite marker loci in the Insulin (INS) gene region.
AB - In a small chromosomal region, a number of polymorphisms may be both linked to and associated with a disease. Distinguishing the potential causal sites from those indirectly associated due to linkage disequilibrium (LD) with a causal site is an important problem. This problem may be approached by determining which of the associations can explain the observed linkage signal. Recently, several methods have been proposed to aid in the identification of disease associated polymorphisms that may explain an observed linkage signal, using genotype data from affected sib pairs (ASPs) [Li et al. [2005] Am. J. Hum. Genet. 76:934-949; Sun et al. [2002] Am. J. Hum. Genet. 70:399-411]. These methods can be used to test the null hypothesis that a candidate single nucleotide polymorphism (SNP) is the sole causal variant in the region, or is in complete LD with the sole causal variant in the region. We extend variations of these methods to test for complete LD between a disease locus and haplotypes composed of two or more tightly linked candidate SNPs. We study properties of the proposed methods by simulation and apply them to type 1 diabetes data for ASPs and their parents at candidate SNP and microsatellite marker loci in the Insulin (INS) gene region.
KW - Association
KW - Conditional tests
KW - Fine mapping
UR - http://www.scopus.com/inward/record.url?scp=36248968736&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36248968736&partnerID=8YFLogxK
U2 - 10.1002/gepi.20236
DO - 10.1002/gepi.20236
M3 - Article
C2 - 17508343
AN - SCOPUS:36248968736
VL - 31
SP - 727
EP - 740
JO - Genetic Epidemiology
JF - Genetic Epidemiology
SN - 0741-0395
IS - 7
ER -