Two-stage genome-wide association study identifies variants in CAMSAP1L1 as susceptibility loci for epilepsy in Chinese

• Published in: Human molecular genetics Vol. 21; no. 5; pp. 1184 - 1189
• Main Authors: Guo, Youling, Baum, Larry W., Sham, Pak Chung, Wong, Virginia, Ng, Ping Wing, Lui, Colin Hiu Tung, Sin, Ngai Chuen, Tsoi, Tak Hong, Tang, Clara S.M., Kwan, Johnny S.H., Yip, Benjamin H.K., Xiao, Su-Mei, Thomas, G. Neil, Lau, Yu Lung, Yang, Wanling, Cherny, Stacey S., Kwan, Patrick
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2012
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Child; Child, Preschool; Cytoskeletal Proteins - genetics; Cytoskeleton; Environmental factors; Epilepsy; Epilepsy - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Glutamic acid receptors; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Male; Medical sciences; Middle Aged; Molecular and cellular biology; Motor task performance; Nervous system (semeiology, syndromes); Neurology; Neurotransmission; Odds Ratio; Polymorphism, Single Nucleotide; Young Adult; Asia; China; Variant; Nervous system diseases; Clinical stage; Genetic variability; Epilepsy; Central nervous system disease; Chinese; Genotype; Genetics; Identification; Locus; Cerebral disorder
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddr550

In the majority of patients, epilepsy is a complex disorder with multiple susceptibility genes interacting with environmental factors. However, we understand little about its genetic risks. Here, we report the first genome-wide association study (GWAS) to identify common susceptibility variants of epilepsy in Chinese. This two-stage GWAS included a total of 1087 patients and 3444 matched controls. In the combined analysis of the two stages, the strongest signals were observed with two highly correlated variants, rs2292096 [G] [P= 1.0 × 10−8, odds ratio (OR) = 0.63] and rs6660197 [T] (P= 9.9 × 10−7, OR = 0.69), with the former reaching genome-wide significance, on 1q32.1 in the CAMSAP1L1 gene, which encodes a cytoskeletal protein. We also refined a previously reported association with rs9390754 (P= 1.7 × 10−5) on 6q21 in the GRIK2 gene, which encodes a glutamate receptor, and identified several other loci in genes involved in neurotransmission or neuronal networking that warrant further investigation. Our results suggest that common genetic variants may increase the susceptibility to epilepsy in Chinese.