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Evidence for linkage of red blood cell size and count: Genome‐wide scans in the Framingham Heart Study
Author(s) -
Lin JingPing,
O'Donnell Christopher J.,
Jin Li,
Fox Caroline,
Yang Qiong,
Cupples L. Adrienne
Publication year - 2007
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20868
Subject(s) - mean corpuscular volume , mean corpuscular hemoglobin , medicine , mean corpuscular hemoglobin concentration , genetic linkage , genetics , framingham heart study , hemoglobin , biology , framingham risk score , gene , disease
Abstract Red blood cell (RBC) count and size are major criteria for evaluating anemia and related hematology disease diagnoses. While environmental factors influence RBC count (RBCC) and size, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), studies have indicated that each of these measures has a substantial genetic component. So far, no linkage analysis or genome scan has been reported. We carried out 10 cM genome‐wide scans on RBCC, MCV, and MCH in a community‐based Caucasian cohort, the Framingham Heart Study, using 325 pedigrees with 1,144 individuals genotyped and phenotyped. Using variance‐component linkage methods, heritabilities were estimated as 56, 52, and 52% after covariate adjusted for RBCC, MCV, and MCH, respectively. For RBCC, we found a maximum LOD score of 3.2 on chromosome 19, 24 cM (7.0 Mbp). Near this region, there lie a few important candidate genes, including erythropoietin receptor and erythroid Krüppel‐like factor. For linkage analyses for MCV and MCH, there were coinciding maximized LOD scores on chromosome 11, 9 cM (5.2 Mbp) with values of 3.8 and 3.6, respectively. Under the peak resides the hemoglobin β cluster ‐ several β‐like genes, which are important candidates for RBC size. In subsequent analyses, we excluded individuals with low MCV to assess the possible influence of β‐thalassemia carriers, and there continued to be evidence for linkage in the same region on chromosome 11p15 (LOD scores of 2.6 and 2.7 for MCV and MCH, respectively). For MCV, we also identified a new region on chromosome 6q24 with a LOD score of 2.9. These findings suggest that further studies are warranted to identify potential causal genetic variants for RBC size and count and related erythrocyte indices. Am. J. Hematol., 2007. Published 2007 Wiley‐Liss, Inc.