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Genetic linkage of human height is confirmed to 9q22 and Xq24

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Abstract

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.

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Acknowledgements

Investigators of this work were partially supported by grants from NIH (K01 AR02170-01, R01 AR45349-01, R01 GM60402-01A1) and an LB595 grant from the State of Nebraska. The study also benefited due to grants from National Science Foundation of China, Huo Ying Dong Education Foundation, HuNan Province, Xi’an Jiaotong University, and the Ministry of Education of China. The genotyping experiment was performed by Marshfield Center for Medical Genetics and supported by NHLBI Mammalian Genotyping Service (Contract Number HV48141).

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Authors and Affiliations

  1. Osteoporosis Research Center, Creighton University Medical Center, 601 N 30th Street, Suite 6787, Omaha, NE, 68131, USA

    Yao-Zhong Liu, Peng Xiao, Yan-fang Guo, Dong-Hai Xiong, Lan-Juan Zhao, Hui Shen, Yong-Jun Liu, Volodymyr Dvornyk, Ji-Rong Long, Hong-Yi Deng, Robert R. Recker & Hong-Wen Deng

  2. Department of Biomedical Sciences, Creighton University, Omaha, NE, 68131, USA

    Yao-Zhong Liu, Peng Xiao, Yan-fang Guo, Dong-Hai Xiong, Lan-Juan Zhao, Hui Shen, Yong-Jun Liu, Volodymyr Dvornyk, Ji-Rong Long & Hong-Wen Deng

  3. The Key Laboratory of Biomedical Information and Engineering, Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, 710049, Xi’an , People’s Republic of China

    Hong-Wen Deng

  4. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, 410081, Changsha, Hunan, People’s Republic of China

    Yan-fang Guo & Hong-Wen Deng

  5. Department of Biological Sciences, Kent State University, Kent, OH, 44242, USA

    Volodymyr Dvornyk

  6. Seattle Biomedical Research Institute, 307 Westlake Ave N, Seattle, WA, 98109, USA

    Jin-Long Li

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  1. Yao-Zhong Liu
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  2. Peng Xiao
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  13. Hong-Wen Deng
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Correspondence to Hong-Wen Deng.

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Liu, YZ., Xiao, P., Guo, Yf. et al. Genetic linkage of human height is confirmed to 9q22 and Xq24 . Hum Genet 119, 295–304 (2006). https://doi.org/10.1007/s00439-006-0136-y

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