Journal article
Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits
Molecular genetics & genomic medicine, Vol.1(3), pp.131-141
09/2013
DOI: 10.1002/mgg3.16
PMCID: PMC3775389
PMID: 24058921
Abstract
We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), and white blood cell count (WBC) using SOLAR. Age and gender were found to be significant covariates in many CBC traits. We obtained significant heritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC. We report four candidate loci with Logarithm of the odds (LOD) scores above 2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We also report eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariate linkage analysis of MCV and MCH on chromosome 20 resulted in a higher maximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22, 6q25, and 20q13 are concomitant with previously reported QTL. All other linkage signals reported herein represent novel evidence of candidate QTL. Interestingly rs1800562, the most common causal variant of hereditary hemochromatosis in
HFE
(6p22) was associated with MCH and MCHC in this family. Linkage studies like the one presented here will allow investigators to focus the search for rare variants amidst the noise encountered in the large amounts of data generated by whole-genome sequencing.
Details
- Title: Subtitle
- Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits
- Creators
- Jesse D Hinckley - Department of Pediatrics and Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical CampusDiana Abbott - Duke Biostatistics Core, Duke UniversityTrudy L Burns - Departments of Epidemiology, College of Public Health, University of IowaMeadow Heiman - Departments of Indiana Hemophilia and Thrombosis CenterAmy D Shapiro - Departments of Indiana Hemophilia and Thrombosis CenterKai Wang - Departments of Biostatistics, College of Public Health, University of IowaJorge Di Paola - Department of Pediatrics and Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus
- Resource Type
- Journal article
- Publication Details
- Molecular genetics & genomic medicine, Vol.1(3), pp.131-141
- Publisher
- Blackwell Publishing Ltd
- DOI
- 10.1002/mgg3.16
- PMID
- 24058921
- PMCID
- PMC3775389
- ISSN
- 2324-9269
- eISSN
- 2324-9269
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 HL084086; name: Postle Family Chair in Pediatric Cancer and Blood Disorders
- Language
- English
- Date published
- 09/2013
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9983997341702771
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