TY - JOUR
T1 - Quantitative trait locus linkage analysis in a large amish pedigree identifies novel candidate loci for erythrocyte traits
AU - Hinckley, Jesse D.
AU - Abbott, Diana
AU - Burns, Trudy L.
AU - Heiman, Meadow
AU - Shapiro, Amy D.
AU - Wang, Kai
AU - Di Paola, Jorge
N1 - Publisher Copyright:
© 2013 The Authors.
PY - 2013/9
Y1 - 2013/9
N2 - We characterized a large Amish pedigree and, in 384 pedigree members, analyzedthe genetic variance components with covariate screen as well as genomewidequantitative 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 hemoglobinconcentration (MCHC), red cell distribution width (RDW), platelet count(PLT), and white blood cell count (WBC) using SOLAR. Age and gender werefound to be significant covariates in many CBC traits. We obtained significantheritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC.We report four candidate loci with Logarithm of the odds (LOD) scores above2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We alsoreport eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariatelinkage analysis of MCV and MCH on chromosome 20 resulted in a highermaximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22,6q25, and 20q13 are concomitant with previously reported QTL. All otherlinkage signals reported herein represent novel evidence of candidate QTL.Interestingly rs1800562, the most common causal variant of hereditary hemochromatosisin HFE (6p22) was associated with MCH and MCHC in thisfamily. Linkage studies like the one presented here will allow investigators tofocus the search for rare variants amidst the noise encountered in the largeamounts of data generated by whole-genome sequencing.
AB - We characterized a large Amish pedigree and, in 384 pedigree members, analyzedthe genetic variance components with covariate screen as well as genomewidequantitative 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 hemoglobinconcentration (MCHC), red cell distribution width (RDW), platelet count(PLT), and white blood cell count (WBC) using SOLAR. Age and gender werefound to be significant covariates in many CBC traits. We obtained significantheritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC.We report four candidate loci with Logarithm of the odds (LOD) scores above2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We alsoreport eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariatelinkage analysis of MCV and MCH on chromosome 20 resulted in a highermaximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22,6q25, and 20q13 are concomitant with previously reported QTL. All otherlinkage signals reported herein represent novel evidence of candidate QTL.Interestingly rs1800562, the most common causal variant of hereditary hemochromatosisin HFE (6p22) was associated with MCH and MCHC in thisfamily. Linkage studies like the one presented here will allow investigators tofocus the search for rare variants amidst the noise encountered in the largeamounts of data generated by whole-genome sequencing.
KW - Amish
KW - Erythrocytes
KW - Linkage
KW - QTL
UR - http://www.scopus.com/inward/record.url?scp=84990252549&partnerID=8YFLogxK
U2 - 10.1002/mgg3.16
DO - 10.1002/mgg3.16
M3 - Article
C2 - 24058921
AN - SCOPUS:84990252549
SN - 2324-9269
VL - 1
SP - 131
EP - 141
JO - Molecular Genetics and Genomic Medicine
JF - Molecular Genetics and Genomic Medicine
IS - 3
ER -