Quantitative trait locus linkage analysis in a large amish pedigree identifies novel candidate loci for erythrocyte traits

Jesse D. Hinckley, Diana Abbott, Trudy L. Burns, Meadow Heiman, Amy D. Shapiro, Kai Wang, Jorge Di Paola

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish
Pages (from-to)131-141
Number of pages11
JournalMolecular Genetics and Genomic Medicine
Issue number3
StatePublished - Sep 2013


  • Amish
  • Erythrocytes
  • Linkage
  • QTL


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