Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis

INDICO Consortium

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Abstract

A recent genome-wide association study (GWAS) identified association with variants in Xlinked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525 - OR 1.71, P = 1.38 x 10-09; rs12008279 - OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220 - OR 1.72, P = 9.20 x 10-09; rs6622126 - OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31-0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.

Original languageEnglish
Article numbere0147345
JournalPLoS One
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

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pancreatitis
Disease Susceptibility
Chronic Pancreatitis
disease resistance
Genes
Alleles
alleles
genes
Genome-Wide Association Study
Gene-Environment Interaction
loci
genotype-environment interaction
alcohol abuse
nationalities and ethnic groups
genotyping
etiology
ancestry
alcohols
Alcohols

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis. / INDICO Consortium.

In: PLoS One, Vol. 11, No. 1, e0147345, 01.01.2016.

Research output: Contribution to journalArticle

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title = "Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis",
abstract = "A recent genome-wide association study (GWAS) identified association with variants in Xlinked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62{\%} and alcoholic in 16.38{\%} of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525 - OR 1.71, P = 1.38 x 10-09; rs12008279 - OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220 - OR 1.72, P = 9.20 x 10-09; rs6622126 - OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95{\%} CI [0.31-0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.",
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T1 - Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis

AU - INDICO Consortium

AU - Giri, Anil K.

AU - Midha, Shallu

AU - Banerjee, Priyanka

AU - Agrawal, Ankita

AU - Mehdi, Syed Jafar

AU - Dhingra, Rajan

AU - Kaur, Ismeet

AU - Kumar, G. Ramesh

AU - Lakhotia, Ritika

AU - Ghosh, Saurabh

AU - Das, Kshaunish

AU - Mohindra, Samir

AU - Rana, Surinder

AU - Bhasin, Deepak K.

AU - Garg, Pramod K.

AU - Bharadwaj, Dwaipayan

AU - Garg, Pramod Kumar

AU - Bhatnagar, Shinjini

AU - Bhasin, Deepak Kumar

AU - Tandon, Nikhil

AU - Mohan, Viswanathan

AU - Sharma, Abhay

AU - Tabassum, Rubina

AU - Mahajan, Anubha

AU - Dwivedi, Om Prakash

AU - Ramakrishnan, Lakshmi

AU - Venkatesan, Radha

AU - Manickam, Chidambaram

AU - Prabhakaran, D.

AU - Reddy, K. S.

AU - Banerjee, Monisha

AU - Saxena, Madhukar

AU - Mathur, Sandeep

AU - Bhansali, Anil

AU - Shah, Viral

AU - Madhu, S. V.

AU - Marwah, R. K.

AU - Venkatesh, Pradeep

AU - Aggarwal, S. K.

AU - Gupta, Shantanu Sen

AU - Chavali, Sreenivas

AU - Sharma, Amitabh

AU - Basu, Analabha

AU - Bandesh, Khushdeep

AU - Chakraborty, Shraddha

AU - Kauser, Yasmeen

AU - Abitha, B.

AU - Undru, Aditya

AU - Rajashekar, Donaka

AU - Parekatt, Vaisak

PY - 2016/1/1

Y1 - 2016/1/1

N2 - A recent genome-wide association study (GWAS) identified association with variants in Xlinked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525 - OR 1.71, P = 1.38 x 10-09; rs12008279 - OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220 - OR 1.72, P = 9.20 x 10-09; rs6622126 - OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31-0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.

AB - A recent genome-wide association study (GWAS) identified association with variants in Xlinked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525 - OR 1.71, P = 1.38 x 10-09; rs12008279 - OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220 - OR 1.72, P = 9.20 x 10-09; rs6622126 - OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31-0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.

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