Electronic Resource
Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
| العنوان: | Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration |
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| المؤلفون: | 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., Nilsson, B., Nielsen, A., Mazzoni, G., Karaderi, T., Rasmussen, S., Johansen, J., Allesøe, R., Fritsche, A., Thorand, B., Adamski, J., Grallert, H., Haid, M., Sharma, S., Troll, M., Adam, J., Ferrer, J., Eriksen, H., Frost, G., Häussler, Ragna S., Hong, Mun-Gwan, Schwenk, Jochen M., Uhlén, Mathias, Nicolay, C., Pavo, I., Steckel-Hamann, B., Thomas, M., Adragni, K., Wu, H., Hart, L., Roderick, S., van Leeuwen, N., Dekkers, K., Frau, F., Gassenhuber, J., Jablonka, B., Musholt, P., Ruetten, H., Tillner, J., Baltauss, T., Bernard Poenaru, O., de Preville, N., Rodriquez, M., Arumugam, M., Allin, K., Engelbrechtsen, L., Hansen, T., Forman, A., Jonsson, A., Pedersen, O., Dutta, A., Vogt, J., Vestergaard, H., Laakso, M., Kokkola, T., Kuulasmaa, T., Franks, P., Giordano, N., Pomares-Millan, H., Fitipaldi, H., Mutie, P., Klintenberg, M., Bergstrom, M., Groop, L., Ridderstrale, M., Atabaki Pasdar, N., Deshmukh, H., Heggie, A., Wake, D., McEvoy, D., McVittie, I., Walker, M., Hattersley, A., Hill, A., Jones, A., McDonald, T., Perry, M., Nice, R., Hudson, M., Thorne, C., Dermitzakis, E., Viñuela, A., Cabrelli, L., Loftus, H., Dawed, A., Donnelly, L., Forgie, I., Pearson, E., Palmer, C., Brown, A., Koivula, R., Wesolowska-Andersen, A., Abdalla, M., McRobert, N., Fernandez, J., Jiao, Y., Robertson, N., Gough, S., Kaye, J., Mourby, M., Mahajan, A., McCarthy, M., Shah, N., Teare, H., Holl, R., Koopman, A., Rutters, F., Beulens, J., Groeneveld, L., Bell, J., Thomas, L., Whitcher, B., Hingorani, A. D., Patel, R. S., Hemingway, H., Franks, P. W., Bell, J. D., Banerjee, R., Yaghootkar, H. |
| بيانات النشر: | KTH, Affinitets-proteomik KTH, Science for Life Laboratory, SciLifeLab 2019 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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 <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart di QC 20191128 |
| مصطلحات الفهرس: | Genetics, Genome-wide association study, Iron, Magnetic resonance imaging, Metabolic syndrome, Metabolism, Gastroenterology and Hepatology, Gastroenterologi, Article in journal, info:eu-repo/semantics/article, text |
| DOI: | 10.1016.j.jhep.2019.05.032 |
| URL: | Journal of Hepatology, 0168-8278, 2019, 71:3, s. 594-602 |
| الاتاحة: | Open access content. Open access content info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | English |
| Other Numbers: | UPE oai:DiVA.org:kth-262512 0000-0003-1664-8875 0000-0001-8603-8293 0000-0001-8141-8449 0000-0002-4858-8056 doi:10.1016/j.jhep.2019.05.032 PMID 31226389 ISI:000481571400017 Scopus 2-s2.0-85068854139 1234980203 |
| المصدر المساهم: | UPPSALA UNIV LIBR From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1234980203 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.1016.j.jhep.2019.05.032 |
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