RESEARCH ARTICLE Genetic Association of ACSM1 Variation with Schizophrenia and Major Depressive Disorder in the Han Chinese Population Wenjin Li, 1,2,3a Weidong Ji, 5a Zhiqiang Li, 1,2,3 Kuanjun He, 1,2,3 Qingzhong Wang, 1,2,3 Jianhua Chen, 1,2,3,4 Yu Qiang, 1,2,3 Guoyin Feng, 4 Xingwang Li, 1 Jiawei Shen, 1,2,3 Zujia Wen, 1,2,3 Jue Ji, 1,2,3 and Yongyong Shi 1,2,3 * 1 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, P.R. China 2 Bio-X Institutes, Key Laboratory of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, P.R. China 3 Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China 4 Shanghai Mental Health Center, Shanghai, P.R. China 5 Shanghai Changning Mental Health Center, Shanghai, P.R. China Manuscript Received: 20 August 2014; Manuscript Accepted: 25 November 2014 Schizophrenia (SCZ) and major depressive disorder (MDD) are two of the most common and severe mental disorders, the etiologies of which are not yet clearly elucidated. The ACSM1 gene has been identified as a susceptibility gene for SCZ in two previous genome- wide association studies (GWAS). ACSM1 catalyzes the activation of fatty acids and plays an important role in the metabolic system. Some evidence has suggested that ACSM1 contributes to a genetic risk for MDD. The present study aimed to evaluate the common genetic risk of the ACSM1 gene in these two disorders in the Han Chinese population. In total, 1235 patients with SCZ, 1045 patients with MDD and 1235 control subjects of Chinese origin were recruited. Six single nuclear polymorphisms (SNPs) in ACSM1 were genotyped to test their associations with SCZ and MDD. SNP rs163234 was found to be significantly associated with both SCZ (permutated P allele ¼ 1.700  10 3 , OR ¼ 1.350 [95% CI ¼ 1.152–1.581]) and MDD (permutated P allele ¼ 4.800  10 3 , OR ¼ 1.329 [95% CI ¼ 1.127– 1.567]). SNP rs433598 showed a strong association with SCZ (per- mutated P allele ¼ 4.300  10 3 , OR ¼ 1.303 [95% CI ¼ 1.117– 1.520]). Haplotype analysis of the blocks containing the two positive markers also revealed a significant association. This is the first study to assess the possible association of the ACSM1 gene with a genetic susceptibility for MDD. Our data are the first to suggest a positive association of the ACSM1 gene with a genetic susceptibility for SCZ and MDD in the Han Chinese population. Ó 2015 Wiley Periodicals, Inc. Key words: Schizophrenia; major depressive disorder; ACSM1; association; SNP INTRODUCTION Psychiatric disorders place a large burden not only on affected individuals and their families but also on society and health services. Schizophrenia (SCZ) and major depressive disorder (MDD) are two of the most common and most severe mental disorders and are consistently related to increased disability. The prevalence of SCZ is up to 1% worldwide, and the lifetime risk of MDD ranges from 5% to 25% [Demyttenaere et al., 2004]. The highest lifetime rates of suicidal behavior were also found in patients with schizoaffective disorder and major depression with psychotic features [Radomsky et al., 1999]. In addition, numerous studies have suggested that SCZ and MDD, similar to other mental illnesses, may be typically complex diseases involving both genetic and environmental factors [Vaswani and Kapur, 2001; Kendler Ks, 2005] with substantial How to Cite this Article: Li W,Ji W, Li Z, He K, Wang Q, Chen J, Qiang Y, Feng G, Li X, Shen J, Wen Z, Ji J, Shi Y. 2015. Genetic Association of ACSM1 Variation with Schizophrenia and Major Depressive Disorder in the Han Chinese Population. Am J Med Genet Part B 168B:144–149. a These authors contributed equally to this paper. Conflict of interest: None.  Correspondence, Address for correspondence: Dr. Yongyong Shi, Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China. E-mail: shiyongyong@gmail.com Article first published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/ajmg.b.32291 Ó 2015 Wiley Periodicals, Inc. 144 Neuropsychiatric Genetics