Genome-Wide Association Analysis Identifies LILRB2 Gene for Pathological Myopia

Lingxi Jiang; Lulin Huang; Chao Dai; Rui Zheng; Masahiro Miyake; Yuki Mori; Shin-Ya Nakao; Kazuya Morino; Kenji Ymashiro; Yang-Bao Miao; Qi Li; Weiming Ren; Zimeng Ye; Hongjing Li; Zhenglin Yang; Yi Shi

doi:10.1002/advs.202308968

Genome-Wide Association Analysis Identifies LILRB2 Gene for Pathological Myopia

Adv Sci (Weinh). 2024 Oct;11(40):e2308968. doi: 10.1002/advs.202308968. Epub 2024 Aug 29.

Authors

Lingxi Jiang^{1

2}, Lulin Huang^{1

2}, Chao Dai¹, Rui Zheng¹, Masahiro Miyake³, Yuki Mori³, Shin-Ya Nakao³, Kazuya Morino³, Kenji Ymashiro³, Yang-Bao Miao¹, Qi Li¹, Weiming Ren¹, Zimeng Ye⁴, Hongjing Li^{1

2}, Zhenglin Yang^{1

2

5}, Yi Shi^{1

2}

Affiliations

¹ Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, China.
² Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, 610072, China.
³ Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
⁴ School of Medicine, University of Sydney, Camperdown, NSW, 2050, Australia.
⁵ Jinfeng Laboratory, Chongqing, China, Chongqing, 400000, China.

Abstract

Pathological myopia (PM) is one of the leading causes of blindness, especially in Asia. To identify the genetic risk factors of PM, a two-stage genome-wide association study (GWAS) and replication analysis in East Asian populations is conducted. The analysis identified LILRB2 in 19q13.42 as a new candidate locus for PM. The increased protein expression of LILRB2/Pirb (mouse orthologous protein) in PM patients and myopia mouse models is validated. It is further revealed that the increase in LILRB2/Pirb promoted fatty acid synthesis and lipid accumulation, leading to the destruction of choroidal function and the development of PM. This study revealed the association between LILRB2 and PM, uncovering the molecular mechanism of lipid metabolism disorders leading to the pathogenesis of PM due to LILRB2 upregulation.

Keywords: GWAS; LILRA3; LILRB2; lipid accumulation; pathological myopia.

MeSH terms

Adult
Animals
Disease Models, Animal
Female
Genetic Predisposition to Disease / genetics
Genome-Wide Association Study* / methods
Humans
Male
Membrane Glycoproteins* / genetics
Membrane Glycoproteins* / metabolism
Mice
Middle Aged
Myopia, Degenerative / genetics
Receptors, Immunologic* / genetics
Receptors, Immunologic* / metabolism

Substances

LILRB2 protein, human
Membrane Glycoproteins
Receptors, Immunologic

Abstract

MeSH terms

Substances

Grants and funding