title: Faster haplotype frequency estimation using unrelated subjects.
abstract: Linkage disequilibrium (LD) between tightly linked loci provides fine mapping information of disease-predisposing allelic variants. The most common method of LD analysis involves unrelated cases and controls. We have previously proposed model-free and permutation tests for diseases with unknown mode of inheritance that can be applied to several highly polymorphic loci. However, performing such analyses remained computer intensive. In this report we propose a speed-up of both the gene-counting procedure and the permutation procedure. We demonstrate the improved method with an analysis of schizophrenia and human leucocyte antigen markers, and an analysis of alcoholism and mitochondrial aldehyde dehydrogenase markers. Our implementation also allows the rapid calculation of permutation-based LD measures and related statistics.
authors.affiliation: Department of Psychological Medicine, Developmental Psychiatry Research Centre, Institute of Psychiatry, Denmark Hill, London, UK. j.zhao@iop.kcl.ac.uk
authors.forename: Jing Hua
authors.initials: JH
authors.lastname: Zhao
authors.forename: Pak Chnng
authors.initials: PC
authors.lastname: Sham
mesh_terms: D000437:Alcoholism / Q000235:genetics; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005787:Gene Frequency; D005819:Genetic Markers; D006680:HLA Antigens; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D012559:Schizophrenia / Q000235:genetics; D013223:Statistics as Topic / Q000379:methods*
chemical_list: D005819:Genetic Markers; D006680:HLA Antigens; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial