scholarly journals Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

2016 ◽  
Vol 2 (6) ◽  
pp. e1501678 ◽  
Author(s):  
Till F. M. Andlauer ◽  
Dorothea Buck ◽  
Gisela Antony ◽  
Antonios Bayas ◽  
Lukas Bechmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genome Wide Association Study ◽  
Immune Cell ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Substructure ◽  
Epigenetic Signatures ◽  
Folate Cycle ◽  
Ms Pathogenesis

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genesL3MBTL3,MAZ,ERG, andSHMT1. The lead variant atSHMT1was replicated in an independent Sardinian cohort. Products of the genesL3MBTL3,MAZ, andERGplay important roles in immune cell regulation.SHMT1encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

scholarly journals A Genome-Wide Association Study in Early COPD: Identification of One Major Susceptibility Loci

2020 ◽  
Vol Volume 15 ◽  
pp. 2967-2975
Author(s):  
Ye-Jin Lee ◽  
SeungHo Choi ◽  
Sung-Youn Kwon ◽  
Yunhwan Lee ◽  
Jung Kyu Lee ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-Wide Association Study of Susceptibility Loci for T-Cell Acute Lymphoblastic Leukemia in Children

2019 ◽  
Vol 111 (12) ◽  
pp. 1350-1357 ◽  
Author(s):  
Maoxiang Qian ◽  
Xujie Zhao ◽  
Meenakshi Devidas ◽  
Wenjian Yang ◽  
Yoshihiro Gocho ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Risk Allele ◽  
Lymphoblastic Leukemia ◽  
Genome Wide Association ◽  
Luciferase Assay ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common cancer in children and can arise in B or T lymphoid lineages. Although risk loci have been identified for B-ALL, the inherited basis of T-ALL is mostly unknown, with a particular paucity of genome-wide investigation of susceptibility variants in large patient cohorts. Methods We performed a genome-wide association study (GWAS) in 1191 children with T-ALL and 12 178 controls, with independent replication using 117 cases and 5518 controls. The associations were tested using an additive logistic regression model. Top risk variants were tested for effects on enhancer activity using luciferase assay. All statistical tests were two sided. Results A novel risk locus in the USP7 gene (rs74010351, odds ratio [OR] = 1.44, 95% confidence interval [CI] = 1.27 to 1.65, P = 4.51 × 10–8) reached genome-wide significance in the discovery cohort, with independent validation (OR = 1.51, 95% CI = 1.03 to 2.22, P = .04). The USP7 risk allele was overrepresented in individuals of African descent, thus contributing to the higher incidence of T-ALL in this race/ethnic group. Genetic changes in USP7 (germline variants or somatic mutations) were observed in 56.4% of T-ALL with TAL1 overexpression, statistically significantly higher than in any other subtypes. Functional analyses suggested this T-ALL risk allele is located in a putative cis-regulatory DNA element with negative effects on USP7 transcription. Finally, comprehensive comparison of 14 susceptibility loci in T- vs B-ALL pointed to distinctive etiology of these leukemias. Conclusions These findings indicate strong associations between inherited genetic variation and T-ALL susceptibility in children and shed new light on the molecular etiology of ALL, particularly commonalities and differences in the biology of the two major subtypes (B- vs T-ALL).

scholarly journals A Genome-Wide Association Study Identifies Potential Susceptibility Loci for Hirschsprung Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110292 ◽  
Author(s):  
Jeong-Hyun Kim ◽  
Hyun Sub Cheong ◽  
Jae Hoon Sul ◽  
Jeong-Meen Seo ◽  
Dae-Yeon Kim ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Hirschsprung Disease ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

scholarly journals Novel Susceptibility Loci for Moyamoya Disease Revealed by a Genome-Wide Association Study

Stroke ◽  
2018 ◽  
Vol 49 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Lian Duan ◽  
Ling Wei ◽  
Yanghua Tian ◽  
Zhengshan Zhang ◽  
Panpan Hu ◽  
...  
Keyword(s):  
Association Study ◽  
Moyamoya Disease ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

A genome-wide association study reveals 2 new susceptibility loci for atopic dermatitis

2015 ◽  
Vol 136 (3) ◽  
pp. 802-806 ◽  
Author(s):  
Heidi Schaarschmidt ◽  
David Ellinghaus ◽  
Elke Rodríguez ◽  
Anja Kretschmer ◽  
Hansjörg Baurecht ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population

2012 ◽  
Vol 44 (4) ◽  
pp. 430-434 ◽  
Author(s):  
Chizu Tanikawa ◽  
Yuji Urabe ◽  
Keitaro Matsuo ◽  
Michiaki Kubo ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Association Study ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome
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