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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration

Authors :
Wilman, Henry R.
Parisinos, Constantinos A.
Atabaki-Pasdar, Naeimeh
Kelly, Matt
Thomas, E. Louise
Neubauer, Stefan
Jennison, Christopher
Ehrhardt, Beate
Baum, Patrick
Schoelsch, Corinna
Freijer, Jan
Grempler, Rolf
Graefe-Mody, Ulrike
Hennige, Anita
Dings, Christiane
Lehr, Thorsten
Scherer, Nina
Sihinecich, Iryna
Pattou, Francois
Raverdi, Violeta
Caiazzo, Robert
Torres, Fanelly
Verkindt, Helene
Mari, Andrea
Tura, Andrea
Giorgino, Toni
Bizzotto
Froguel, Philippe
Bonneford, Amelie
Canouil, Mickael
Dhennin, Veronique
Brorsson, Caroline
Brunak, Soren
de Masi, Federico
Gudmundsdóttir, Valborg
Pedersen, Helle
Banasik, Karina
Thomas, Cecilia
Sackett, Peter
Staerfeldt, Hans-Henrik
Lundgaard, Agnete
Koopman, Anitra
Rutters, Femke
Beulens, Joline
Groeneveld, Lenka
Thomas, Louise
Whitcher, Brandon
Mahajan, Anubha
Hingorani, Aroon D.
Patel, Riyaz S.
Hemingway, Harry
Franks, Paul W.
Bell, Jimmy D.
Banerjee, Rajarshi
Yaghootkar, Hanieh
Epidemiology and Data Science
APH - Health Behaviors & Chronic Diseases
ACS - Diabetes & metabolism
ACS - Heart failure & arrhythmias
APH - Aging & Later Life
Source :
Journal of Hepatology, 71(3), 594-602. Elsevier, Wilman, H R, Parisinos, C A, Atabaki-Pasdar, N, Kelly, M, Thomas, E L, Neubauer, S, Jennison, C, Ehrhardt, B, Baum, P, Schoelsch, C, Freijer, J, Grempler, R, Graefe-Mody, U, Hennige, A, Dings, C, Lehr, T, Scherer, N, Sihinecich, I, Pattou, F, Raverdi, V, Caiazzo, R, Torres, F, Verkindt, H, Mari, A, Tura, A, Giorgino, T, Bizzotto, Froguel, P, Bonneford, A, Canouil, M, Dhennin, V, Brorsson, C, Brunak, S, de Masi, F, Gudmundsdóttir, V, Pedersen, H, Banasik, K, Thomas, C, Sackett, P, Staerfeldt, H-H, Lundgaard, A, Koopman, A, Rutters, F, Beulens, J, Groeneveld, L, IMI DIRECT Consortium, Koopman, A, Rutters, F, Beulens, J, Groeneveld, L, Koopman, A, Thomas, L, Whitcher, B, Mahajan, A, Hingorani, A D, Patel, R S, Hemingway, H, Franks, P W, Bell, J D, Banerjee, R & Yaghootkar, H 2019, ' Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration ', Journal of Hepatology, vol. 71, no. 3, pp. 594-602 . https://doi.org/10.1016/j.jhep.2019.05.032
Publication Year :
2019

Abstract

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p

Details

Language :
English
ISSN :
01688278
Database :
OpenAIRE
Journal :
Journal of Hepatology, 71(3), 594-602. Elsevier, Wilman, H R, Parisinos, C A, Atabaki-Pasdar, N, Kelly, M, Thomas, E L, Neubauer, S, Jennison, C, Ehrhardt, B, Baum, P, Schoelsch, C, Freijer, J, Grempler, R, Graefe-Mody, U, Hennige, A, Dings, C, Lehr, T, Scherer, N, Sihinecich, I, Pattou, F, Raverdi, V, Caiazzo, R, Torres, F, Verkindt, H, Mari, A, Tura, A, Giorgino, T, Bizzotto, Froguel, P, Bonneford, A, Canouil, M, Dhennin, V, Brorsson, C, Brunak, S, de Masi, F, Gudmundsdóttir, V, Pedersen, H, Banasik, K, Thomas, C, Sackett, P, Staerfeldt, H-H, Lundgaard, A, Koopman, A, Rutters, F, Beulens, J, Groeneveld, L, IMI DIRECT Consortium, Koopman, A, Rutters, F, Beulens, J, Groeneveld, L, Koopman, A, Thomas, L, Whitcher, B, Mahajan, A, Hingorani, A D, Patel, R S, Hemingway, H, Franks, P W, Bell, J D, Banerjee, R & Yaghootkar, H 2019, ' Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration ', Journal of Hepatology, vol. 71, no. 3, pp. 594-602 . https://doi.org/10.1016/j.jhep.2019.05.032
Accession number :
edsair.dedup.wf.001..21d8f03cbd3e4487af956734fab22e15
Full Text :
https://doi.org/10.1016/j.jhep.2019.05.032