Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

Ellen A. Tsai; Christopher M. Grochowski; Kathleen M. Loomes; Kazuhiko Bessho; Hakon Hakonarson; Jorge A. Bezerra; Pierre A. Russo; Barbara A. Haber; Nancy B. Spinner; Marcella Devoto

doi:10.1007/s00439-013-1368-2

Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

Ellen A. Tsai, Christopher M. Grochowski, Kathleen M. Loomes, Kazuhiko Bessho, Hakon Hakonarson, Jorge A. Bezerra, Pierre A. Russo, Barbara A. Haber, Nancy B. Spinner, Marcella Devoto

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61 Scopus citations

Abstract

In the United States, biliary atresia (BA) is the most frequent indication for liver transplantation in pediatric patients. BA is a complex disease, with suspected environmental and genetic risk factors. A genome-wide association study in Chinese patients identified association to the 10q24.2 (hg18) genomic region. This signal was upstream of two genes, XPNPEP1 and ADD3, both expressed in intrahepatic bile ducts. We tested association to this region in 171 BA patients and 1,630 controls of European descent and found the strongest signal to be at rs7099604 (p = 2.5 × 10^-3) in intron 1 of the ADD3 gene. Moreover, expression data suggest that ADD3, but not XPNPEP1, is differentially expressed in BA patients. The role of ADD3 in biliary development is unclear, but our findings suggest that this gene may be functionally relevant for the development of BA.

Original language	English (US)
Pages (from-to)	235-243
Number of pages	9
Journal	Human genetics
Volume	133
Issue number	2
DOIs	https://doi.org/10.1007/s00439-013-1368-2
State	Published - Feb 2014
Externally published	Yes

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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title = "Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia",

abstract = "In the United States, biliary atresia (BA) is the most frequent indication for liver transplantation in pediatric patients. BA is a complex disease, with suspected environmental and genetic risk factors. A genome-wide association study in Chinese patients identified association to the 10q24.2 (hg18) genomic region. This signal was upstream of two genes, XPNPEP1 and ADD3, both expressed in intrahepatic bile ducts. We tested association to this region in 171 BA patients and 1,630 controls of European descent and found the strongest signal to be at rs7099604 (p = 2.5 × 10-3) in intron 1 of the ADD3 gene. Moreover, expression data suggest that ADD3, but not XPNPEP1, is differentially expressed in BA patients. The role of ADD3 in biliary development is unclear, but our findings suggest that this gene may be functionally relevant for the development of BA.",

author = "Tsai, {Ellen A.} and Grochowski, {Christopher M.} and Loomes, {Kathleen M.} and Kazuhiko Bessho and Hakon Hakonarson and Bezerra, {Jorge A.} and Russo, {Pierre A.} and Haber, {Barbara A.} and Spinner, {Nancy B.} and Marcella Devoto",

year = "2014",

month = feb,

doi = "10.1007/s00439-013-1368-2",

language = "English (US)",

volume = "133",

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T1 - Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

AU - Tsai, Ellen A.

AU - Grochowski, Christopher M.

AU - Loomes, Kathleen M.

AU - Bessho, Kazuhiko

AU - Hakonarson, Hakon

AU - Bezerra, Jorge A.

AU - Russo, Pierre A.

AU - Haber, Barbara A.

AU - Spinner, Nancy B.

AU - Devoto, Marcella

PY - 2014/2

Y1 - 2014/2

N2 - In the United States, biliary atresia (BA) is the most frequent indication for liver transplantation in pediatric patients. BA is a complex disease, with suspected environmental and genetic risk factors. A genome-wide association study in Chinese patients identified association to the 10q24.2 (hg18) genomic region. This signal was upstream of two genes, XPNPEP1 and ADD3, both expressed in intrahepatic bile ducts. We tested association to this region in 171 BA patients and 1,630 controls of European descent and found the strongest signal to be at rs7099604 (p = 2.5 × 10-3) in intron 1 of the ADD3 gene. Moreover, expression data suggest that ADD3, but not XPNPEP1, is differentially expressed in BA patients. The role of ADD3 in biliary development is unclear, but our findings suggest that this gene may be functionally relevant for the development of BA.

AB - In the United States, biliary atresia (BA) is the most frequent indication for liver transplantation in pediatric patients. BA is a complex disease, with suspected environmental and genetic risk factors. A genome-wide association study in Chinese patients identified association to the 10q24.2 (hg18) genomic region. This signal was upstream of two genes, XPNPEP1 and ADD3, both expressed in intrahepatic bile ducts. We tested association to this region in 171 BA patients and 1,630 controls of European descent and found the strongest signal to be at rs7099604 (p = 2.5 × 10-3) in intron 1 of the ADD3 gene. Moreover, expression data suggest that ADD3, but not XPNPEP1, is differentially expressed in BA patients. The role of ADD3 in biliary development is unclear, but our findings suggest that this gene may be functionally relevant for the development of BA.

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Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

Abstract

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