title: Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis.
abstract: To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, Pcombined = 2.92 × 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, Pcombined = 2.35 × 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
authors.affiliation: Medical Research Center, Peking University Third Hospital, Beijing, China.
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authors.lastname: van den Berg
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authors.lastname: Liu
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mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000235:genetics*; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D002892:Chromosomes, Human, Pair 22; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008562:Membrane Glycoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D008562:Membrane Glycoproteins; C582626:SUSD2 protein, human; C517603:CAMK1G protein, human; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1