Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung’s Disease in Han Chinese Population
Background and Aims: Hirschsprung’s disease (HSCR) is a rare genetically heterogeneous congenital disorder. A recent study based on whole genome sequencing demonstrated that common variants at four novel loci, which contained two intronic variants on CASQ2 and PLD1, and intergenic variants located b...
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2020-07-01
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English |
format |
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DOAJ |
author |
Wei-Bo Niu Wei-Bo Niu Wei-Bo Niu Mei-Rong Bai Mei-Rong Bai Mei-Rong Bai Huan-Lei Song Huan-Lei Song Huan-Lei Song Yan-Jiao Lu Yan-Jiao Lu Yan-Jiao Lu Wen-Jie Wu Wen-Jie Wu Wen-Jie Wu Yi-Ming Gong Yi-Ming Gong Yi-Ming Gong Xian-Xian Yu Xian-Xian Yu Xian-Xian Yu Zhi-Liang Wei Zhi-Liang Wei Zhi-Liang Wei Wen-Wen Yu Wen-Wen Yu Wen-Wen Yu Bei-Lin Gu Bei-Lin Gu Bei-Lin Gu Wei Cai Wei Cai Wei Cai Xun Chu Xun Chu Xun Chu |
spellingShingle |
Wei-Bo Niu Wei-Bo Niu Wei-Bo Niu Mei-Rong Bai Mei-Rong Bai Mei-Rong Bai Huan-Lei Song Huan-Lei Song Huan-Lei Song Yan-Jiao Lu Yan-Jiao Lu Yan-Jiao Lu Wen-Jie Wu Wen-Jie Wu Wen-Jie Wu Yi-Ming Gong Yi-Ming Gong Yi-Ming Gong Xian-Xian Yu Xian-Xian Yu Xian-Xian Yu Zhi-Liang Wei Zhi-Liang Wei Zhi-Liang Wei Wen-Wen Yu Wen-Wen Yu Wen-Wen Yu Bei-Lin Gu Bei-Lin Gu Bei-Lin Gu Wei Cai Wei Cai Wei Cai Xun Chu Xun Chu Xun Chu Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung’s Disease in Han Chinese Population Frontiers in Genetics association Hirschsprung’s disease case-control study single nucleotide polymorphisms Han Chinese population |
author_facet |
Wei-Bo Niu Wei-Bo Niu Wei-Bo Niu Mei-Rong Bai Mei-Rong Bai Mei-Rong Bai Huan-Lei Song Huan-Lei Song Huan-Lei Song Yan-Jiao Lu Yan-Jiao Lu Yan-Jiao Lu Wen-Jie Wu Wen-Jie Wu Wen-Jie Wu Yi-Ming Gong Yi-Ming Gong Yi-Ming Gong Xian-Xian Yu Xian-Xian Yu Xian-Xian Yu Zhi-Liang Wei Zhi-Liang Wei Zhi-Liang Wei Wen-Wen Yu Wen-Wen Yu Wen-Wen Yu Bei-Lin Gu Bei-Lin Gu Bei-Lin Gu Wei Cai Wei Cai Wei Cai Xun Chu Xun Chu Xun Chu |
author_sort |
Wei-Bo Niu |
title |
Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung’s Disease in Han Chinese Population |
title_short |
Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung’s Disease in Han Chinese Population |
title_full |
Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung’s Disease in Han Chinese Population |
title_fullStr |
Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung’s Disease in Han Chinese Population |
title_full_unstemmed |
Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung’s Disease in Han Chinese Population |
title_sort |
association of variants in pld1, 3p24.1, and 10q11.21 regions with hirschsprung’s disease in han chinese population |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2020-07-01 |
description |
Background and Aims: Hirschsprung’s disease (HSCR) is a rare genetically heterogeneous congenital disorder. A recent study based on whole genome sequencing demonstrated that common variants at four novel loci, which contained two intronic variants on CASQ2 and PLD1, and intergenic variants located between SLC4A7 and EOMES at 3p24.1, and between LINC01518 and LOC283028 at 10q11.21, were associated with HSCR susceptibility. To validate these associations with HSCR susceptibility, we performed a case–control study in a Han Chinese sample set.Methods: We selected four previously identified single nucleotide polymorphisms (SNPs) for replication, along with tag SNPs to cover the four associated regions. In total, 61 SNPs were genotyped in 420 HSCR patients and 1,665 healthy controls from the Han Chinese population.Results: None of the 14 tag SNPs in the CASQ2 gene region, including the previously associated rs9428225, showed an association with HSCR. Among the 24 tag SNPs from the SLC4A7-EOMES region at 3p24.1, rs2642925 [odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 1.10–1.79; PAdditive = 0.007] and the previously associated SNP rs9851320 showed a suggestive association (OR = 1.22, 95% CI = 1.01–1.47; PAdditive = 0.042). A non-synonymous SNP, rs2287579, in PLD1 showed a suggestive association with HSCR susceptibility (OR = 1.71, 95% CI = 1.18–2.46; PAdditive = 0.004). Additionally, the previously associated PLD1 SNP rs12632766 showed a suggestive significance (OR = 1.20, 95% CI = 1.01–1.42, PAdditive = 0.038). In the LINC01518-LOC283028 region at 10q11.21, three SNPs meet the study-wide significance threshold. Rs17153309 was the most associated SNP (OR = 1.60, 95% CI = 1.34–1.90; PAdditive = 1.13 × 10–7). The previously associated SNP rs1414027 also showed significant association (OR = 1.43, 95% CI = 1.20–1.70, PAdditive = 3.92 × 10–5). Two associated SNPs at 10q11.21 (rs1414027 and rs624804) were expression quantitative trait loci in digestive tract tissues from GTEx databases.Conclusions: Our results confirmed that variants of the LINC01518-LOC283028 region were associated with HSCR in the Han Chinese population. Additionally, the susceptibility of SNPs in the LINC01518-LOC283028 region were associated with the expression levels of nearby genes. These results provide new insight into the pathogenesis of HSCR. |
topic |
association Hirschsprung’s disease case-control study single nucleotide polymorphisms Han Chinese population |
url |
https://www.frontiersin.org/article/10.3389/fgene.2020.00738/full |
work_keys_str_mv |
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doaj-6fd21b4b5aee46e98091bc3b4977cdd12020-11-25T02:54:30ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-07-011110.3389/fgene.2020.00738516729Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung’s Disease in Han Chinese PopulationWei-Bo Niu0Wei-Bo Niu1Wei-Bo Niu2Mei-Rong Bai3Mei-Rong Bai4Mei-Rong Bai5Huan-Lei Song6Huan-Lei Song7Huan-Lei Song8Yan-Jiao Lu9Yan-Jiao Lu10Yan-Jiao Lu11Wen-Jie Wu12Wen-Jie Wu13Wen-Jie Wu14Yi-Ming Gong15Yi-Ming Gong16Yi-Ming Gong17Xian-Xian Yu18Xian-Xian Yu19Xian-Xian Yu20Zhi-Liang Wei21Zhi-Liang Wei22Zhi-Liang Wei23Wen-Wen Yu24Wen-Wen Yu25Wen-Wen Yu26Bei-Lin Gu27Bei-Lin Gu28Bei-Lin Gu29Wei Cai30Wei Cai31Wei Cai32Xun Chu33Xun Chu34Xun Chu35Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, ChinaShanghai Institute of Pediatric Research, Shanghai, ChinaBackground and Aims: Hirschsprung’s disease (HSCR) is a rare genetically heterogeneous congenital disorder. A recent study based on whole genome sequencing demonstrated that common variants at four novel loci, which contained two intronic variants on CASQ2 and PLD1, and intergenic variants located between SLC4A7 and EOMES at 3p24.1, and between LINC01518 and LOC283028 at 10q11.21, were associated with HSCR susceptibility. To validate these associations with HSCR susceptibility, we performed a case–control study in a Han Chinese sample set.Methods: We selected four previously identified single nucleotide polymorphisms (SNPs) for replication, along with tag SNPs to cover the four associated regions. In total, 61 SNPs were genotyped in 420 HSCR patients and 1,665 healthy controls from the Han Chinese population.Results: None of the 14 tag SNPs in the CASQ2 gene region, including the previously associated rs9428225, showed an association with HSCR. Among the 24 tag SNPs from the SLC4A7-EOMES region at 3p24.1, rs2642925 [odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 1.10–1.79; PAdditive = 0.007] and the previously associated SNP rs9851320 showed a suggestive association (OR = 1.22, 95% CI = 1.01–1.47; PAdditive = 0.042). A non-synonymous SNP, rs2287579, in PLD1 showed a suggestive association with HSCR susceptibility (OR = 1.71, 95% CI = 1.18–2.46; PAdditive = 0.004). Additionally, the previously associated PLD1 SNP rs12632766 showed a suggestive significance (OR = 1.20, 95% CI = 1.01–1.42, PAdditive = 0.038). In the LINC01518-LOC283028 region at 10q11.21, three SNPs meet the study-wide significance threshold. Rs17153309 was the most associated SNP (OR = 1.60, 95% CI = 1.34–1.90; PAdditive = 1.13 × 10–7). The previously associated SNP rs1414027 also showed significant association (OR = 1.43, 95% CI = 1.20–1.70, PAdditive = 3.92 × 10–5). Two associated SNPs at 10q11.21 (rs1414027 and rs624804) were expression quantitative trait loci in digestive tract tissues from GTEx databases.Conclusions: Our results confirmed that variants of the LINC01518-LOC283028 region were associated with HSCR in the Han Chinese population. Additionally, the susceptibility of SNPs in the LINC01518-LOC283028 region were associated with the expression levels of nearby genes. These results provide new insight into the pathogenesis of HSCR.https://www.frontiersin.org/article/10.3389/fgene.2020.00738/fullassociationHirschsprung’s diseasecase-control studysingle nucleotide polymorphismsHan Chinese population |