Epistasis between loci on chromosomes 2 and 6 influences human height.
BACKGROUND
Human height is a typical and important complex trait, which is determined by both actions and interactions of multiple genes. Although an increasing number of genes or genomic regions have been discovered for their independent effects on height variation, no study has been performed to identify genes or loci that interact to control the trait.


OBJECTIVE
This study aimed to search for potential genomic regions that harbor interactive genes underlying human height.


METHODS
Here with a sample containing 3726 Caucasians, the largest one ever obtained from a single population of the same ethnicity among genetic linkage studies of human complex traits, we performed variance component linkage analyses of height based on a two-locus epistatic model. We examined pairwise genetic interaction among three regions, 9q22, 6p21, and 2q21, which achieved significant or suggestive linkage signals for height in our recent whole genome scan.


RESULTS
Significant genetic interaction between 6p21 and 2q21 was detected, with 2q21 achieving a maximum LOD score of 3.21 (P = 0.0035) under the epistatic model, compared with a maximum LOD score of 1.63 under a two-locus additive model. Interestingly, 6p21 contains a cluster of candidate genes for skeletal growth, suggesting a mechanism whereby 2q21 regulates height through 6p21.


CONCLUSIONS
By providing the first evidence for genetic interaction underlying human height variation, this study further delineated the genetic architecture of human height and contributed to the genetic dissection of human complex traits in general.
Liu
Yao-Zhong
YZ
Osteoporosis Research Center, Creighton University Medical Center, 601 North 30th Street, Suite 6787, Omaha, NE 68131, USA.
Guo
Yan-Fang
YF
Xiao
Peng
P
Xiong
Dong-Hai
DH
Zhao
Lan-Juan
LJ
Shen
Hui
H
Liu
Yong-Jun
YJ
Dvornyk
Volodymyr
V
Long
Ji-Rong
JR
Deng
Hong-Yi
HY
Li
Jin-Long
JL
Deng
Hong-Wen
HW
D000328:Adult; D000368:Aged; D001827:Body Height / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2; D002896:Chromosomes, Human, Pair 6; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged