Genome-Wide Association Study Identifies ALDH7A1 as a Novel Susceptibility Gene for Osteoporosis

Second-generation antipsychotics (SGAs) play a critical role in current treatment of schizophrenia (SCZ). It has been observed that sinus bradycardia, rare but in certain situations life threatening adverse drug reaction, can be induced by SGAs across different schizophrenia populations. However, the roles of genetic factors in this phenomenon have not been studied yet. In the present study, a genome-wide association study of single nucleotide polymorphisms (SNPs) was performed on Chinese Han SCZ patients to identify susceptibility loci that were associated with sinus bradycardia induced by SGAs. This study applied microarray to obtain genotype profiles of 88 Han Chinese SCZ patients. Our results found that there were no SNPs had genome-wide significant association with sinus bradycardia induced by SGAs. The top GWAS hit located in gene KIAA0247, which mainly regulated by the tumor suppressor P53 and thus plays a role in carcinogenesis based on resent research and it should not be a susceptibility locus to sinus bradycardia induced by SGAs. Using gene-set functional analysis, we tested that if top 500 SNPs mapped genes were relevant to sinus bradycardia. The result of gene prioritization analysis showed CTNNA3 was strongly correlated with sinus bradycardia, hinting it was a susceptibility gene of this ADR. Our study provides a preliminary study of genetic variants associated with sinus bradycardia induced by SGAs in Han Chinese SCZ patients. The discovery of a possible susceptibility gene shed light on further study of this adverse drug reaction in Han Chinese SCZ patients.

Download Full-text

ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study

The Lancet Neurology ◽

10.1016/s1474-4422(07)70222-3 ◽

2007 ◽

Vol 6 (10) ◽

pp. 869-877 ◽

Cited By ~ 141

Author(s):

Michael A van Es ◽

Paul W Van Vught ◽

Hylke M Blauw ◽

Lude Franke ◽

Christiaan G Saris ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Association Study ◽

Genome Wide Association Study ◽

Susceptibility Gene ◽

Genome Wide Association ◽

Sporadic Amyotrophic Lateral Sclerosis ◽

Genome Wide ◽

A Genome ◽

Lateral Sclerosis

Download Full-text

Genome-wide association study identifies TNFSF13 as a susceptibility gene for IgA in a South Chinese population in smokers

Immunogenetics ◽

10.1007/s00251-012-0636-y ◽

2012 ◽

Vol 64 (10) ◽

pp. 747-753 ◽

Cited By ~ 21

Author(s):

Chen Yang ◽

Wang Jie ◽

Yang Yanlong ◽

Guo Xuefeng ◽

Tan Aihua ◽

...

Keyword(s):

Association Study ◽

Chinese Population ◽

Genome Wide Association Study ◽

Susceptibility Gene ◽

Genome Wide Association ◽

Genome Wide

Download Full-text

Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CLBL genes

Multiple Sclerosis Journal ◽

10.1177/1352458511432741 ◽

2011 ◽

Vol 18 (7) ◽

pp. 959-965 ◽

Cited By ~ 20

Author(s):

Jezabel Varadé ◽

Manuel Comabella ◽

Miguel A Ortiz ◽

Rafael Arroyo ◽

Oscar Fernández ◽

...

Keyword(s):

Multiple Sclerosis ◽

Autoimmune Diseases ◽

Association Study ◽

Genome Wide Association Study ◽

Susceptibility Gene ◽

Pooled Analysis ◽

Replication Study ◽

Genome Wide Association ◽

Genome Wide

Background and objectives: Ten genes previously showing different evidence of association with multiple sclerosis have been selected to validate. Methods: Eleven polymorphisms were genotyped with the iPLEX™ Sequenom in a well-powered collection of Spanish origin including 2863 multiple sclerosis cases and 2930 controls. Results: Replication extended to the following polymorphisms: PKN2 (rs305217), GTF2B (rs7538427), EPHA4 (rs1517440), YTHDF3 (rs12115114), ANKFN1 (rs17758761) and PTPRM (rs4798571), which did not reach the threshold of significance in a follow-up of the first genome-wide association study (GWAS) conducted in multiple sclerosis; TMEM39A (rs1132200), which appeared as a newly identified susceptibility gene in the same study; a gene previously reaching GWAS significance in Italy, CBLB (rs9657904); IL12B (rs6887695, rs10045431), a susceptibility gene shared by diverse autoimmune diseases and, finally, another gene showing inconclusive association with multiple sclerosis, CNR1 (rs1049353). Conclusions: Pooled analysis corroborated the effect on MS predisposition of three genes: TMEM39A [rs1132200: pM-H=0.001; ORM-H (95% CI)= 0.84 (0.75–0.93)], IL12B [rs6887695: pM-H=0.03; ORM-H (95% CI)= 1.09 (1.01–1.17)] and CBLB [rs9657904: pM-H=0.01; ORM-H (95% CI)= 0.89 (0.81–0.97)].

Download Full-text