Genome-wide linkage of forced mid-expiratory flow in chronic obstructive pulmonary disease.
Familial aggregation of forced expiratory flow during the middle half of the FVC (FEF(25-75%)) and FEF(25-75%)/FVC has been observed in the Boston Early-Onset Chronic Obstructive Pulmonary Disease Study, but linkage results have not been reported for these phenotypes. An autosomal whole genome-wide linkage scan was performed in 72 pedigrees ascertained through a proband with severe, early-onset chronic obstructive pulmonary disease, and linkage analyses of FEF(25-75%) and FEF(25-75%)/FVC were performed using Sequential Oligogenic Linkage Analysis Routines. There was suggestive evidence for linkage of FEF(25-75%)/FVC with chromosome 2 (LOD 2.60 at 216 cM). In a smokers-only analysis, evidence for linkage was observed for postbronchodilator FEF(25-75%) with chromosome 12 (LOD 5.03 at 35 cM) and chromosomes 2 and 12 for FEF(25-75%)/FVC (LOD 4.12 at 221 cM and LOD 3.46 at 35 cM, respectively); in the smokers-only model, evidence for linkage also was robust for FEV(1)/FVC on chromosome 2 (LOD 4.13 at 229 cM) and FEV(1) on chromosome 12 (LOD 3.26 at 36 cM). Our analyses provide evidence for linkage of FEF(25-75%) and FEF(25-75%)/FVC on chromosomes 2q and 12p. LOD scores of greater than two were also observed for chromosomes 16, 20, and 22 with the smokers-only analysis, which may suggest gene-by-smoking interactions in these regions.
DeMeo
Dawn L
DL
Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. redld@channing.harvard.edu
Celedón
Juan C
JC
Lange
Christoph
C
Reilly
John J
JJ
Chapman
Harold A
HA
Sylvia
Jody S
JS
Speizer
Frank E
FE
Weiss
Scott T
ST
Silverman
Edwin K
EK
D000328:Adult; D000368:Aged; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008297:Male; D008450:Maximal Midexpiratory Flow Rate; D008875:Middle Aged; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology*