NELL-1 in Genome-Wide Association Studies across Human Diseases

Xu Cheng; Jiayu Shi; Zhonglin Jia; Pin Ha; Chia Soo; Kang Ting; Aaron W James; Bing Shi; Xinli Zhang

doi:10.1016/j.ajpath.2021.11.006

NELL-1 in Genome-Wide Association Studies across Human Diseases

Am J Pathol. 2022 Mar;192(3):395-405. doi: 10.1016/j.ajpath.2021.11.006. Epub 2021 Dec 7.

Authors

Xu Cheng¹, Jiayu Shi², Zhonglin Jia³, Pin Ha², Chia Soo⁴, Kang Ting⁵, Aaron W James⁶, Bing Shi⁷, Xinli Zhang⁸

Affiliations

¹ State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Diseases, and the Department of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California-Los Angeles, Los Angeles, California.
² Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California-Los Angeles, Los Angeles, California.
³ State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Diseases, and the Department of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
⁴ Division of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, University of California-Los Angeles, Los Angeles, California.
⁵ Forsyth Institute, affiliate of the Harvard School of Dental Medicine, Boston, Massachusetts.
⁶ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁷ State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Diseases, and the Department of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: shibingcn1@126.com.
⁸ Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California-Los Angeles, Los Angeles, California. Electronic address: xzhang@dentistry.ucla.edu.

Abstract

Neural epidermal growth factor-like (EGFL)-like protein (NELL)-1 is a potent and key osteogenic factor in the development and regeneration of skeletal tissues. Intriguingly, accumulative data from genome-wide association studies (GWASs) have started unveiling potential broader roles of NELL-1 beyond its functions in bone and cartilage. With exploration of the genetic variants of the entire genome in large-scale disease cohorts, GWASs have been used for establishing the connection between specific single-nucleotide polymorphisms of NELL1, in addition to osteoporosis, metabolic diseases, inflammatory conditions, neuropsychiatric diseases, neurodegenerative disorders, and malignant tumors. This review summarizes the findings from GWASs on the manifestation, significance level, implications on function, and correlation of specific NELL1 single-nucleotide polymorphisms in various disorders in humans. By offering a unique and comprehensive correlation between genetic variants and plausible functions of NELL1 in GWASs, this review illustrates the wide range of potential effects of a single gene on the pathogenesis of multiple disorders in humans.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Calcium-Binding Proteins* / genetics
Calcium-Binding Proteins* / metabolism
Cartilage
Genome-Wide Association Study*
Humans
Osteogenesis
Osteoporosis*
Polymorphism, Single Nucleotide

Substances

Calcium-Binding Proteins
NELL1 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding