Quantitative linkage genome scan for atopy in a large collection of Caucasian families.
Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early adulthood, asthma is frequently associated also with quantitative measures of atopy. Genome wide quantitative multipoint linkage analysis was conducted for serum IgE levels and percentage of positive skin prick test (SPT(per)) using three large groups of families originally ascertained for asthma. In this report, 438 and 429 asthma families were informative for linkage using IgE and SPT(per) which represents 690 independent families. Suggestive linkage (LOD > or = 2) was found on chromosomes 1, 3, and 8q with maximum LODs of 2.34 (IgE), 2.03 (SPT(per)), and 2.25 (IgE) near markers D1S1653, D3S2322-D3S1764, and D8S2324, respectively. The results from chromosomes 1 and 3 replicate previous reports of linkage. We also replicate linkage to 5q with peak LODs of 1.96 (SPT(per)) and 1.77 (IgE) at or near marker D5S1480. Our results provide further evidence implicating chromosomes 1, 3, and 5q. The current report represents one of the biggest genome scans so far reported for asthma related phenotypes. This study also demonstrates the utility of increased sample sizes and quantitative phenotypes in linkage analysis of complex disorders.
Webb
Bradley T
BT
Virginia Institute for Psychiatric and Behavioral Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
van den Oord
Edwin
E
Akkari
Anthony
A
Wilton
Steve
S
Ly
Tina
T
Duff
Rachael
R
Barnes
Kathleen C
KC
Carlsen
Karin
K
Gerritsen
Jorrit
J
Lenney
Warren
W
Silverman
Michael
M
Sly
Peter
P
Sundy
John
J
Tsanakas
John
J
von Berg
Andrea
A
Whyte
Moira
M
Blumenthal
Malcolm
M
Vestbo
Jorgen
J
Middleton
Lefkos
L
Helms
Peter J
PJ
Anderson
Wayne H
WH
Pillai
Sreekumar G
SG
D000293:Adolescent; D000328:Adult; D000818:Animals; D001249:Asthma / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012882:Skin Tests; D044465:White People