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Updated: Jan 1, 2026

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
Identification of TYW3/CRYZ and FGD4 as susceptibility genes for amyotrophic lateral sclerosis
Ling Wei1, Yanghua Tian1, Yongping Chen1
1Department 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.
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.

