AB0021 A genome-wide snp linkage analysis suggests a novel susceptibility gene for ankylosing spondylitis

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.

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A genome-wide linkage analysis of dementia in the Amish

American Journal of Medical Genetics Part B Neuropsychiatric Genetics ◽

10.1002/ajmg.b.30257 ◽

2006 ◽

Vol 141B (2) ◽

pp. 160-166 ◽

Cited By ~ 29

Author(s):

Daniel W. Hahs ◽

Jacob L. McCauley ◽

Amy E. Crunk ◽

Lynne L. McFarland ◽

Perry C. Gaskell ◽

...

Keyword(s):

Linkage Analysis ◽

Genome Wide ◽

A Genome

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A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjy197 ◽

2018 ◽

Vol 13 (5) ◽

pp. 648-658 ◽

Cited By ~ 8

Author(s):

Yoichi Kakuta ◽

Yosuke Kawai ◽

Takeo Naito ◽

Atsushi Hirano ◽

Junji Umeno ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Mononuclear Cells ◽

Association Studies ◽

Susceptibility Gene ◽

Genome Wide Association ◽

Effector Memory ◽

Genome Wide Association Studies ◽

Genome Wide ◽

A Genome

Abstract Background and Aims Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn’s disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel. Methods Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions. Results Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10−26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10−19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10−6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10−8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression. Conclusions RAP1A is a novel susceptibility locus for CD in the Japanese population.

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A genome-wide sib-pair linkage analysis of ossification of the posterior longitudinal ligament of the spine

Journal of Bone and Mineral Metabolism ◽

10.1007/s00774-012-0404-y ◽

2012 ◽

Vol 31 (2) ◽

pp. 136-143 ◽

Cited By ~ 17

Author(s):

Tatsuki Karasugi ◽

◽

Masahiro Nakajima ◽

Katsunori Ikari ◽

Takashi Tsuji ◽

...

Keyword(s):

Linkage Analysis ◽

Posterior Longitudinal Ligament ◽

Genome Wide ◽

A Genome

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A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia

Blood ◽

10.1182/blood-2007-05-091561 ◽

2007 ◽

Vol 110 (9) ◽

pp. 3326-3333 ◽

Cited By ~ 53

Author(s):

Gabrielle S. Sellick ◽

Lynn R. Goldin ◽

Ruth W. Wild ◽

Susan L. Slager ◽

Laura Ressenti ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Familial Aggregation ◽

Susceptibility Gene ◽

Snp Array ◽

High Density ◽

Lymphocytic Leukemia ◽

Nonparametric Model ◽

Model Free ◽

Genome Wide ◽

A Genome

Abstract Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders display familial aggregation. To identify a susceptibility gene for CLL, we assembled families from the major European (ICLLC) and American (GEC) consortia to conduct a genome-wide linkage analysis of 101 new CLL pedigrees using a high-density single nucleotide polymorphism (SNP) array and combined the results with data from our previously reported analysis of 105 families. Here, we report on the combined analysis of the 206 families. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. After the removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage (NPL) score of 3.02 (P = .001) on chromosome 2q21.2. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a common recessive model of disease susceptibility (HLOD = 3.11; P = 7.7 × 10−5), which was significant at the genome-wide level. In addition, 2 other chromosomal positions, 6p22.1 (corresponding to the major histocompatibility locus) and 18q21.1, displayed HLOD scores higher than 2.1 (P < .002). None of the regions coincided with areas of common chromosomal abnormalities frequently observed in CLL. These findings provide direct evidence for Mendelian predisposition to CLL and evidence for the location of disease loci.

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