Genome-wide association study of bipolar I disorder in the Han Chinese population

Lee, M T M; Chen, C H; Lee, C S; Chen, C C; Chong, Mian‐Yoon; Ouyang, Wen‐Chen; Chiu, Nan‐Ying; Chuo, Liang-Jen; Chen, C Y; Tan, Happy Kuy‐Lok; Lane, Hsien‐Yuan; Chang, T J; Lin, Ching‐Hua; Jou, Shaw-Hwa; Hou, Yuh‐Ming; Feng, Jung; Lai, Te-Jen; Tung, Chun‐Liang; Chen, T J; Chang, Ching‐Jui; Lung, For‐Wey; Chen, C K; Shiah, I‐Shin; Liu, C Y; Teng, Po Ren; Chen, K H; Shen, Ling-xun; Cheng, Chih-Ya; Chang, Tien-Jyun; Li, C F; Chou, Ching‐Heng; Wang, K H T; Fann, Cathy S.J.; Wu, Jer‐Yuarn; Chen, Y T; Cheng, Andrew T. A.

doi:10.1038/mp.2010.43

Cited by 136 publications

(132 citation statements)

References 31 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…For example, a number of loss-of-function mutations of ankyrin-R are known to cause hereditary spherocytosis (9). Genetic variants of ankyrin-G are associated with bipolar disorder (10)(11)(12)(13)(14). Many missense mutations of ankyrin-B have been linked to inherited cardiac arrhythmia known as the "ankyrin-B syndrome" (15).…”

mentioning

confidence: 99%

Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals interaction surfaces necessary for ankyrin function

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Ankyrin-R/B/G (encoded by ANK1/2/3, respectively) are a family of very large scaffold proteins capable of anchoring numerous receptors and ion channels to specific, spectrin-containing membrane micro-domains. Hereditary mutations of ankyrins are known to be associated with diseases including spherocytosis, cardiac arrhythmia, and bipolar disorder in humans, although the underlying molecular bases are poorly understood. The middle spectrin-binding domain of ankyrins contains highly conserved ZU5-ZU5-UPA-DD domains arranged into the ZZUD tandem. Curiously, most of the disease-causing mutations in the tandem have no apparent impact on the spectrin binding of ankyrins. The high resolution structure of the ankyrin-B ZZUD tandem determined here reveals that the ZU5-ZU5-UPA domains form a tightly packed structural supramodule, whereas DD is freely accessible. Although the formation of the ZZU supramodule does not influence the spectrin binding of ankyrins, mutations altering the interdomain interfaces of ZZU impair the functions of ankyrin-B&G. Our structural analysis further indicates that the ZZU supramodule of ankyrins has two additional surfaces that may bind to targets other than spectrin. Finally, the structure of the ankyrin ZZUD provides mechanistic explanations to many disease-causing mutations identified in ankyrin-B&R.A nkyrins are a family of adaptor proteins required for the construction and maintenance of specialized membrane domains in various tissues via anchoring specific membrane proteins to spectrin-based cytoskeletons (see refs. 1 and 2 for reviews). Vertebrates contain three ankyrins: ankyrin-R, -B, and -G, all containing an N-terminal membrane-binding domain (MBD), a central spectrin-binding domain (SBD), a death domain (DD) with ill-defined functions, and a variable C-terminal regulatory domain (2) (Fig. 1C). Ankyrin-R, the first identified ankyrin from erythrocytes, is also expressed in other tissues (3, 4). Ankyrin-B, originally identified in brain, functions in many tissues including in the cardiac and skeletal muscles (2). Ankyrin-G, the most broadly expressed ankyrin, is critical for the formation and stabilization of axon initial segments of neurons, the biogenesis of lateral membrane domains of epithelia as well as other tissue functions (2, 5-8). Loss-of-function mutations in ankyrins are associated with hereditary diseases in humans. For example, a number of loss-of-function mutations of ankyrin-R are known to cause hereditary spherocytosis (9). Genetic variants of ankyrin-G are associated with bipolar disorder (10-14). Many missense mutations of ankyrin-B have been linked to inherited cardiac arrhythmia known as the "ankyrin-B syndrome" (15). Curiously, although MBD is responsible for binding to most of known ankyrin-association proteins, most of the ankyrin-B syndrome mutations are located in the SBD, DD, and regulatory domains, and these mutations do not seem to affect the binding of ankyrins to spectrin (16). These findings suggest that SBD is involved in functions other than binding...

show abstract

mentioning

confidence: 99%

Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals interaction surfaces necessary for ankyrin function

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…ANK3 was confirmed as associated with BD by a study involving individuals from Caucasian and African ancestry. Notably, this study found association with different SNPs in individuals of European and African ancestry [64], and studies in Japanese and Han Chinese populations showed no genome-wide significant findings [65,66].…”

Section: Genome-wide Association Studies In Bipolar Disordermentioning

confidence: 52%

Genome-Wide Searches for Bipolar Disorder Genes

Alsabban

Rivera

McGuffin

2011

Curr Psychiatry Rep

View full text Add to dashboard Cite

Whole-genome linkage and association studies of bipolar disorder are beginning to provide some compelling evidence for the involvement of several chromosomal regions and susceptibility genes in the pathogenesis of bipolar disorder. Developments in genotyping technology and efforts to combine data from different studies have helped in identifying chromosomes 6q16-q25, 13q, and 16p12 as probable susceptibility loci for bipolar disorder and confirmed CACNA1C and ANK3 as susceptibility genes for bipolar disorder. However, a lack of replication is still apparent in the literature. New studies focusing on copy number variants as well as new analytical approaches utilizing pathway analysis offer a new direction in the study of the genetics of bipolar disorder.

show abstract

“…This region had been reported in two previous genome-wide linkage scans of Eastern Quebec and Northeast Italian families as a common susceptibility region for both schizophrenia and bipolar disorder (Maziade et al, 2005;Vazza et al, 2007). Furthermore, previous studies reported that SNPs of the ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 gene (ST8SIA2), located around 2.5 Mb proximal to the linkage peak (rs2028299) on chromosome 15q26.1, were associated with schizophrenia or bipolar I disorder in Asian population (Arai et al, 2006;Tao et al, 2007;Lee et al, 2011). However, this region did not show evidence of linkage for schizophrenia in our previous genome-wide linkage scan (Hong et al, 2009).…”

Section: Discussionmentioning

confidence: 95%

Genome-wide linkage scan of quantitative traits representing symptom dimensions in multiplex schizophrenia families

Ryu

Won

et al. 2013

Psychiatry Research

View full text Add to dashboard Cite

Genome-wide association study of bipolar I disorder in the Han Chinese population

Cited by 136 publications

References 31 publications

Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals interaction surfaces necessary for ankyrin function

Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals interaction surfaces necessary for ankyrin function

Genome-Wide Searches for Bipolar Disorder Genes

Genome-wide linkage scan of quantitative traits representing symptom dimensions in multiplex schizophrenia families

Contact Info

Product

Resources

About