title: Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the Multiethnic Cohort Study.
abstract: We describe an approach for picking haplotype-tagging single nucleotide polymorphisms (htSNPs) that is presently being taken in two large nested case-control studies within a multiethnic cohort (MEC), which are engaged in a search for associations between risk of prostate and breast cancer and common genetic variations in candidate genes. Based on a preliminary sample of 70 control subjects chosen at random from each of the 5 ethnic groups in the MEC we estimate haplotype frequencies using a variant of the Excoffier-Slatkin E-M algorithm after genotyping a high density of SNPs selected every 3-5 kb in and surrounding a candidate gene. In order to evaluate the performance of a candidate set of htSNPS (which will be genotyped in the much larger case-control sample) we treat the haplotype frequencies estimate above as known, and carry out a formal calculation of the uncertainty of the number of copies of common haplotypes carried by an individual, summarizing this calculation as a coefficient of determination, R2h. A candidate set of htSNPS of a given size is chosen so as to maximize the minimum value of R2h over the common haplotypes, h.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, Calif. 90033, USA. stram@usc.edu
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
mesh_terms: D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D003198:Computer Simulation; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics
chemical_list: D001141:Aromatase