Common variants on chromosome 6p22.1 are associated with schizophrenia

By Jianxin Shi, Doug Levinson, J. Duan, A. Sanders, Yonglan Zheng, Itsik Pe'er, Frank Dudbridge, P. Holmans, Alice S Whittemore, B. Mowry and 13 more. Nature, 2009

1,203 citations recorded by the source corpus.

Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5–1%, with high heritability (80–85%) and complex transmission. Recent studies implicate rare, large, high-penetrance copy number variants in some cases, but the genes or biological mechanisms that underlie susceptibility are not known. Here we show that schizophrenia is significantly associated with single nucleotide polymorphisms (SNPs) in the extended major histocompatibility complex region on chromosome 6. We carried out a genome-wide association study of common SNPs in the Molecular Genetics of Schizophrenia (MGS) case-control sample, and then a meta-analysis of data from the MGS, International Schizophrenia Consortium and SGENE data sets. No MGS finding achieved genome-wide statistical significance. In the meta-analysis of European-ancestry subjects (8,008 cases, 19,077 controls), significant association with schizophrenia was observed in a region of linkage disequilibrium on chromosome 6p22.1 (P = 9.54 × 10-9). This region includes a histone gene cluster and several immunity-related genes—possibly implicating aetiological mechanisms involving chromatin modification, transcriptional regulation, autoimmunity and/or infection. These results demonstrate that common schizophrenia susceptibility alleles can be detected. The characterization of these signals will suggest important directions for research on susceptibility mechanisms.

Subfields: Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/3fc7ac4ede3b595fc3741c6b57ee547bfd202cad

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Surgery

Citations in the corpus

Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs (2012, neutral): “GWAS of schizophrenia have discovered associated variant”
Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia (2017, neutral): “62 8 9255004, 1923090; 9246431, 1998873; (14) (17) 63 8 16036469, 1998029; 16036260, 1999890; (14) (14) 64 8 25465390, 1807196; 25273907, 1998679; (9) (12) 65 8 38021982, 288929; 38020408, 279217; (7) (7) 66 8 60482795, 394183; 59694660, 1998797; 0 (5) 67 8 89188454, 572710; 88265473, 1999263; (1) (”
The role of immune dysfunction in the pathophysiology of autism (2011, neutral): “In addition, two large GWAS studies in schizophrenia highlight changes within the MHC region on chromosome 6 (Shi et al., 2009; Stefansson et al., 2009).”
Uncovering the roles of rare variants in common disease through whole-genome sequencing (2010, background): “3, despite a heritability of 80–85% for schizophreni”
Research review: Polygenic methods and their application to psychiatric traits. (2014, background): “The trajectory of GWAS discovery for schizophrenia, which increased from 1 locus (ISC 2009; Shi et al., 2009) to 7 (Ripke et al.”
Power and Predictive Accuracy of Polygenic Risk Scores (2013, methodology): “In their main result, odds ratios for 74062 nearly independent SNPs were estimated in 3322 cases and 3587 controls and used to construct a polygenic score that was tested in 2687 cases and 2656 controls of the Molecular Genetics of Schizophrenia study [26].”
The diagnosis of mental disorders: the problem of reification. (2010, neutral): “2008, 2009; Morrow et al. 2008; O’Donovan et al. 2008; Shi et al. 2009; T. Walsh et al. 2008; Weiss et al. 2008; Xu et al. 2008).”