Identification of TYW3/CRYZ and FGD4 as susceptibility genes for amyotrophic lateral sclerosis

Ling Wei; Yanghua Tian; Yongping Chen; Qianqian Wei; Fangfang Chen; Bei Cao; Ying Wu; Bi Zhao; Xueping Chen; Chengjuan Xie; Chunhua Xi; Xu'en Yu; Juan Wang; Xinyi Lv; Jing Du; Yu Wang; Lu Shen; Xin Wang; Bin Shen; Qihao Guo; Li Guo; Kun Xia; Peng Xie; Xuejun Zhang; Xianbo Zuo; Huifang Shang; Kai Wang

doi:10.1212/NXG.0000000000000375

Identification of TYW3/CRYZ and FGD4 as susceptibility genes for amyotrophic lateral sclerosis

Neurol Genet. 2019 Nov 8;5(6):e375. doi: 10.1212/NXG.0000000000000375. eCollection 2019 Dec.

Authors

Ling Wei¹, Yanghua Tian¹, Yongping Chen¹, Qianqian Wei¹, Fangfang Chen¹, Bei Cao¹, Ying Wu¹, Bi Zhao¹, Xueping Chen¹, Chengjuan Xie¹, Chunhua Xi¹, Xu'en Yu¹, Juan Wang¹, Xinyi Lv¹, Jing Du¹, Yu Wang¹, Lu Shen¹, Xin Wang¹, Bin Shen¹, Qihao Guo¹, Li Guo¹, Kun Xia¹, Peng Xie¹, Xuejun Zhang¹, Xianbo Zuo¹, Huifang Shang¹, Kai Wang¹

Affiliation

¹ Department of Neurology (L.W., Y.T., C. Xie, Y. Wang, K.W.), the First Affiliated Hospital of Anhui Medical University, Hefei; Department of Neurology (Y.C., Q.W., B.C., Y. Wu, B.Z., X.C., H.S.), West China Hospital of Sichuan University, Chengdu; Department of Medical Psychology (F.C., K.W.), Anhui Medical University; Department of Neurology (C. Xi), the Third Affiliated Hospital of Anhui Medical University; Institution of Neurology (X.Y.), Anhui College of Traditional Medicine; Department of Neurology (J.W.), the Second People's Hospital of Hefei; Department of Neurology (X.L.), Anhui Provincial Hospital; Department of Neurology (J.D.), the Second Affiliated Hospital of Anhui Medical University, Hefei; Department of Neurology (L.S.), Xiangya Hospital of Central South University, Changsha; Department of Neurology (X.W.), Zhongshan Hospital of Fudan University, Shanghai; Department of Physiology (B.S.), School of Basic Medicine, Anhui Medical University, Hefei; Department of Neurology (Q.G.), Huashan Hospital of Fudan University, Shanghai; Department of Neurology (L.G.), the Second Hospital of Hebei Medical University, Shijiazhuang; School of Life Science (K.X.), Central South University, Changsha; Department of Neurology (P.X.), the First Affiliated Hospital of Chongqing Medical University, Chongqing; Department of Dermatology (X. Zhang, X. Zuo), the First Affiliated Hospital of Anhui Medical University; and State Key Laboratory Incubation Base of Dermatology (X. Zhang, X. Zuo), Ministry of National Science and Technology, Hefei, China.

Abstract

Objective: A 2-stage genome-wide association was conducted to explore the genetic etiology of amyotrophic lateral sclerosis (ALS) in the Chinese Han population.

Methods: Totally, 700 cases and 4,027 controls were genotyped in the discovery stage using Illumina Human660W-Quad BeadChips. Top associated single nucleotide polymorphisms from the discovery stage were then genotyped in an independent cohort with 884 cases and 5,329 controls. Combined analysis was conducted by combining all samples from the 2 stages.

Results: Two novel loci, 1p31 and 12p11, showed strong associations with ALS. These novel loci explained 2.2% of overall variance in disease risk. Expression quantitative trait loci searches identified TYW/CRYZ and FGD4 as risk genes at 1p13 and 12p11, respectively.

Conclusions: This study identifies novel susceptibility genes for ALS. Identification of TYW3/CRYZ in the current study supports the notion that insulin resistance may be involved in ALS pathogenesis, whereas FGD4 suggests an association with Charcot-Marie-Tooth disease.