Using linkage and association to identify and model genetic effects: summary of GAW15 Group 4.
Group 4 at Genetic Analysis Workshop 15 focused on methods that exploited both linkage and association information to map disease loci. All contributions considered the dichotomous trait of rheumatoid arthritis, using either affected sibpairs and/or unrelated controls. While one contribution investigated linkage and association approaches separately in genome-wide analyses, the remaining others focused on joint linkage and association methods in specific genomic regions. The latter contributions proposed new methods and/or examined existing methods that addressed whether one or more polymorphisms partially or fully explained a linkage signal, particularly the methods proposed by Li et al. that are implemented in the computer program Linkage and Association Modeling in Pedigrees (LAMP). Using simulated SNP data under linkage peaks, several contributions found that existing family-based association approaches such as those of Martin et al. and Lake et al. had power similar to LAMP and to several methods proposed by the contributors for testing that a single nucleotide polymorphism partially explains a linkage peak. In evaluating methods for identifying if a polymorphism or a set of polymorphisms fully accounted for a linkage signal, several contributions found that it was important to understand that these methods may be subject to low power in some situations and thus, a non-significant result was not necessarily indicative of the polymorphism(s) being fully responsible for the linkage signal. Finally, modeling the disease using association evidence conditional on linkage may improve understanding of the etiology of disease.
Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA. qyang@bu.edu
Qiong
Q
Yang
Joanna M
JM
Biernacka
Ming-Huei
MH
Chen
Jeanine J
JJ
Houwing-Duistermaat
Tracy L
TL
Bergemann
Saonli
S
Basu
Ruzong
R
Fan
Lian
L
Liu
Mathieu
M
Bourgey
Françoise
F
Clerget-Darpoux
Wan-Yu
WY
Lin
Robert C
RC
Elston
L Adrienne
LA
Cupples
Victor
V
Apprey
Jing
J
Cui
Josée
J
Dupuis
Iuliana
I
Ionita-Laza
Rui
R
Li
Xuemei
X
Lou
Hervé
H
Perdry
Richard
R
Sherva
Yin Yao
YY
Shugart
Brian
B
Suarez
Hongling
H
Wang
Hanna
H
Wormald
Guan
G
Xing
Chao
C
Xing
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D011110:Polymorphism, Genetic