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Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis. / Ghouse, Jonas; Sveinbjörnsson, Gardar; Vujkovic, Marijana; Seidelin, Anne-Sofie; Gellert-Kristensen, Helene; Ahlberg, Gustav; Tragante, Vinicius; Rand, Søren A; Brancale, Joseph; Vilarinho, Silvia; Lundegaard, Pia Rengtved; Sørensen, Erik; Erikstrup, Christian; Bruun, Mie Topholm; Jensen, Bitten Aagaard; Brunak, Søren; Banasik, Karina; Ullum, Henrik; Verweij, Niek; Lotta, Luca; Baras, Aris; Mirshahi, Tooraj; Carey, David J; Kaplan, David E; Lynch, Julie; Morgan, Timothy; Schwantes-An, Tae-Hwi; Dochtermann, Daniel R; Pyarajan, Saiju; Tsao, Philip S; Laisk, Triin; Mägi, Reedik; Kozlitina, Julia; Tybjærg-Hansen, Anne; Jones, David; Knowlton, Kirk U; Nadauld, Lincoln; Ferkingstad, Egil; Björnsson, Einar S; Ulfarsson, Magnus O; Sturluson, Árni; Sulem, Patrick; Pedersen, Ole B; Ostrowski, Sisse R; Gudbjartsson, Daniel F; Stefansson, Kari; Olesen, Morten Salling; Chang, Kyong-Mi; Bundgaard, Henning; Stender, Stefan; DBDS Genomic Consortium.
I:
Nature Genetics, Bind 56, 2024, s. 827–837.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
Ghouse, J, Sveinbjörnsson, G, Vujkovic, M, Seidelin, A-S, Gellert-Kristensen, H
, Ahlberg, G, Tragante, V, Rand, SA, Brancale, J, Vilarinho, S
, Lundegaard, PR, Sørensen, E, Erikstrup, C, Bruun, MT, Jensen, BA
, Brunak, S, Banasik, K, Ullum, H, Verweij, N, Lotta, L, Baras, A, Mirshahi, T, Carey, DJ, Kaplan, DE, Lynch, J, Morgan, T, Schwantes-An, T-H, Dochtermann, DR, Pyarajan, S, Tsao, PS, Laisk, T, Mägi, R, Kozlitina, J
, Tybjærg-Hansen, A, Jones, D, Knowlton, KU, Nadauld, L, Ferkingstad, E, Björnsson, ES, Ulfarsson, MO, Sturluson, Á, Sulem, P
, Pedersen, OB, Ostrowski, SR, Gudbjartsson, DF, Stefansson, K
, Olesen, MS, Chang, K-M
, Bundgaard, H, Stender, S & DBDS Genomic Consortium 2024, '
Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis',
Nature Genetics, bind 56, s. 827–837.
https://doi.org/10.1038/s41588-024-01720-y
APA
Ghouse, J., Sveinbjörnsson, G., Vujkovic, M., Seidelin, A-S., Gellert-Kristensen, H.
, Ahlberg, G., Tragante, V., Rand, S. A., Brancale, J., Vilarinho, S.
, Lundegaard, P. R., Sørensen, E., Erikstrup, C., Bruun, M. T., Jensen, B. A.
, Brunak, S., Banasik, K., Ullum, H., Verweij, N., ... DBDS Genomic Consortium (2024).
Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.
Nature Genetics,
56, 827–837.
https://doi.org/10.1038/s41588-024-01720-y
Vancouver
Ghouse J, Sveinbjörnsson G, Vujkovic M, Seidelin A-S, Gellert-Kristensen H
, Ahlberg G o.a.
Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.
Nature Genetics. 2024;56:827–837.
https://doi.org/10.1038/s41588-024-01720-y
Author
Ghouse, Jonas ; Sveinbjörnsson, Gardar ; Vujkovic, Marijana ; Seidelin, Anne-Sofie ; Gellert-Kristensen, Helene ; Ahlberg, Gustav ; Tragante, Vinicius ; Rand, Søren A ; Brancale, Joseph ; Vilarinho, Silvia ; Lundegaard, Pia Rengtved ; Sørensen, Erik ; Erikstrup, Christian ; Bruun, Mie Topholm ; Jensen, Bitten Aagaard ; Brunak, Søren ; Banasik, Karina ; Ullum, Henrik ; Verweij, Niek ; Lotta, Luca ; Baras, Aris ; Mirshahi, Tooraj ; Carey, David J ; Kaplan, David E ; Lynch, Julie ; Morgan, Timothy ; Schwantes-An, Tae-Hwi ; Dochtermann, Daniel R ; Pyarajan, Saiju ; Tsao, Philip S ; Laisk, Triin ; Mägi, Reedik ; Kozlitina, Julia ; Tybjærg-Hansen, Anne ; Jones, David ; Knowlton, Kirk U ; Nadauld, Lincoln ; Ferkingstad, Egil ; Björnsson, Einar S ; Ulfarsson, Magnus O ; Sturluson, Árni ; Sulem, Patrick ; Pedersen, Ole B ; Ostrowski, Sisse R ; Gudbjartsson, Daniel F ; Stefansson, Kari ; Olesen, Morten Salling ; Chang, Kyong-Mi ; Bundgaard, Henning ; Stender, Stefan ; DBDS Genomic Consortium. / Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis. I: Nature Genetics. 2024 ; Bind 56. s. 827–837.
Bibtex
@article{f76cd9d7464c4e9cbaab91defc70d686,
title = "Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis",
abstract = "We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.",
author = "Jonas Ghouse and Gardar Sveinbj{\"o}rnsson and Marijana Vujkovic and Anne-Sofie Seidelin and Helene Gellert-Kristensen and Gustav Ahlberg and Vinicius Tragante and Rand, {S{\o}ren A} and Joseph Brancale and Silvia Vilarinho and Lundegaard, {Pia Rengtved} and Erik S{\o}rensen and Christian Erikstrup and Bruun, {Mie Topholm} and Jensen, {Bitten Aagaard} and S{\o}ren Brunak and Karina Banasik and Henrik Ullum and Niek Verweij and Luca Lotta and Aris Baras and Tooraj Mirshahi and Carey, {David J} and Kaplan, {David E} and Julie Lynch and Timothy Morgan and Tae-Hwi Schwantes-An and Dochtermann, {Daniel R} and Saiju Pyarajan and Tsao, {Philip S} and Triin Laisk and Reedik M{\"a}gi and Julia Kozlitina and Anne Tybj{\ae}rg-Hansen and David Jones and Knowlton, {Kirk U} and Lincoln Nadauld and Egil Ferkingstad and Bj{\"o}rnsson, {Einar S} and Ulfarsson, {Magnus O} and {\'A}rni Sturluson and Patrick Sulem and Pedersen, {Ole B} and Ostrowski, {Sisse R} and Gudbjartsson, {Daniel F} and Kari Stefansson and Olesen, {Morten Salling} and Kyong-Mi Chang and Henning Bundgaard and Stefan Stender and {DBDS Genomic Consortium}",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
doi = "10.1038/s41588-024-01720-y",
language = "English",
volume = "56",
pages = "827–837",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
}
RIS
TY - JOUR
T1 - Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis
AU - Ghouse, Jonas
AU - Sveinbjörnsson, Gardar
AU - Vujkovic, Marijana
AU - Seidelin, Anne-Sofie
AU - Gellert-Kristensen, Helene
AU - Ahlberg, Gustav
AU - Tragante, Vinicius
AU - Rand, Søren A
AU - Brancale, Joseph
AU - Vilarinho, Silvia
AU - Lundegaard, Pia Rengtved
AU - Sørensen, Erik
AU - Erikstrup, Christian
AU - Bruun, Mie Topholm
AU - Jensen, Bitten Aagaard
AU - Brunak, Søren
AU - Banasik, Karina
AU - Ullum, Henrik
AU - Verweij, Niek
AU - Lotta, Luca
AU - Baras, Aris
AU - Mirshahi, Tooraj
AU - Carey, David J
AU - Kaplan, David E
AU - Lynch, Julie
AU - Morgan, Timothy
AU - Schwantes-An, Tae-Hwi
AU - Dochtermann, Daniel R
AU - Pyarajan, Saiju
AU - Tsao, Philip S
AU - Laisk, Triin
AU - Mägi, Reedik
AU - Kozlitina, Julia
AU - Tybjærg-Hansen, Anne
AU - Jones, David
AU - Knowlton, Kirk U
AU - Nadauld, Lincoln
AU - Ferkingstad, Egil
AU - Björnsson, Einar S
AU - Ulfarsson, Magnus O
AU - Sturluson, Árni
AU - Sulem, Patrick
AU - Pedersen, Ole B
AU - Ostrowski, Sisse R
AU - Gudbjartsson, Daniel F
AU - Stefansson, Kari
AU - Olesen, Morten Salling
AU - Chang, Kyong-Mi
AU - Bundgaard, Henning
AU - Stender, Stefan
AU - DBDS Genomic Consortium
N1 - © 2024. The Author(s).
PY - 2024
Y1 - 2024
N2 - We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.
AB - We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.
U2 - 10.1038/s41588-024-01720-y
DO - 10.1038/s41588-024-01720-y
M3 - Journal article
C2 - 38632349
VL - 56
SP - 827
EP - 837
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
