Genetic linkage of human height is confirmed to 9q22 and Xq24.
Human height is an important and heritable trait. Our previous two genome-wide linkage studies using 630 (WG1 study) and an extended sample of 1,816 Caucasians (WG2 study) identified 9q22 [maximum LOD score (MLS)=2.74 in the WG2 study] and preliminarily confirmed Xq24 (two-point LOD score=1.91 in the WG1 study, 2.64 in the WG2 study) linked to height. Here, with a much further extended large sample containing 3,726 Caucasians, we performed a new genome-wide linkage scan and confirmed, in high significance, the two regions' linkage to height. An MLS of 4.34 was detected on 9q22 and a two-point LOD score of 5.63 was attained for Xq24. In an independent sub-sample (i.e., the subjects not involved in the WG1 and WG2 studies), the two regions also achieved significant empirical P values (0.002 and 0.004, respectively) for "region-wise" linkage confirmation. Importantly, the two regions were replicated on a genotyping platform different from the WG1 and WG2 studies (i.e., a different set of markers and different genotyping instruments). Interestingly, 9q22 harbors the ROR2 gene, which is required for growth plate development, and Xq24 was linked to short stature. With the largest sample from a single population of the same ethnicity in the field of linkage studies for complex traits, our current study, together with two previous ones, provided overwhelming evidence substantiating 9q22 and Xq24 for height variation. In particular, our three consecutive whole genome studies are uniquely valuable as they represent the first practical (rather than simulated) example of how significant increase in sample size may improve linkage detection for human complex traits.
Liu
Yao-Zhong
YZ
Osteoporosis Research Center, Creighton University Medical Center, 601 N 30th Street, Suite 6787, Omaha, NE 68131, USA.
Xiao
Peng
P
Guo
Yan-fang
YF
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
Recker
Robert R
RR
Deng
Hong-Wen
HW
D000328:Adult; D000368:Aged; D001827:Body Height / Q000235:genetics*; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D041321:Chromosomes, Human, X; D005190:Family; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D040582:Inheritance Patterns; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D040641:Quantitative Trait Loci