A rare variant in COL11A1 is strongly associated with adult height in Chinese Han population

Changbing Shen; Xiaodong Zheng; Jing Gao; Caihong Zhu; Randy Ko; Xianfa Tang; Chao Yang; Jinfa Dou; Yan Lin; Yuyan Cheng; Lu Liu; Shuangjun Xu; Gang Chen; Xianbo Zuo; Xianyong Yin; Liangdan Sun; Yong Cui; Sen Yang; Xuejun Zhang; Fusheng Zhou

doi:10.1016/j.jgg.2016.04.002

A rare variant in COL11A1 is strongly associated with adult height in Chinese Han population

J Genet Genomics. 2016 Sep 20;43(9):549-554. doi: 10.1016/j.jgg.2016.04.002. Epub 2016 Apr 4.

Authors

Changbing Shen¹, Xiaodong Zheng¹, Jing Gao², Caihong Zhu¹, Randy Ko³, Xianfa Tang¹, Chao Yang¹, Jinfa Dou¹, Yan Lin¹, Yuyan Cheng¹, Lu Liu¹, Shuangjun Xu¹, Gang Chen¹, Xianbo Zuo¹, Xianyong Yin⁴, Liangdan Sun¹, Yong Cui⁵, Sen Yang¹, Xuejun Zhang⁶, Fusheng Zhou⁷

Affiliations

¹ Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei 230032, China; Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei 230032, China.
² Department of Dermatology, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, China.
³ Department of Biochemistry, University of New Mexico, Albuquerque, NM 87131, USA.
⁴ Department of Genetics, Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, USA.
⁵ Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China.
⁶ Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei 230032, China; Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei 230032, China; Department of Dermatology, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, China. Electronic address: [email protected].
⁷ Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei 230032, China; Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].

PMID: 27614704
DOI: 10.1016/j.jgg.2016.04.002

Abstract

Human height is a highly heritable trait in which multiple genes are involved. Recent genome-wide association studies (GWASs) have identified that COL11A1 is an important susceptibility gene for human height. To determine whether the variants of COL11A1 are associated with adult and children height, we analyzed splicing and coding single-nucleotide variants across COL11A1 through exome-targeted sequencing and two validation stages with a total 20,426 Chinese Han samples. A total of 105 variants were identified by exome-targeted sequencing, of which 30 SNPs were located in coding region. The strongest association signal was Chr1_103380393 with P value of 4.8 × 10(-7). Chr1_103380393 also showed nominal significance in the validation stage (P = 1.21 × 10(-6)). Combined analysis of 16,738 samples strengthened the original association of chr1_103380393 with adult height (Pcombined = 3.1 × 10(-8)), with an increased height of 0.292sd (standard deviation) per G allele (95% CI: 0.19-0.40). There was no evidence (P = 0.843) showing that chr1_103380393 altered child height in 3688 child samples. Only the group of 12-15 years showed slight significance with P value of 0.0258. This study firstly shows that genetic variants of COL11A1 contribute to adult height in Chinese Han population but not to children height, which expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.

Keywords: Adult height; COL11A1; Chinese Han population; Rare variant.

MeSH terms

Adolescent
Adult
Body Height / genetics*
Child
Child, Preschool
China / ethnology
Collagen Type XI / genetics*
Ethnicity / genetics*
Female
Humans
Infant
Infant, Newborn
Male
Polymorphism, Single Nucleotide*

Substances

COL11A1 protein, human
Collagen Type XI