Refereed review article in scientific journal (A2)

Identification of 90 NAFLD GWAS loci and establishment of NAFLD PRS and causal role of NAFLD in coronary artery disease




List of Authors: Miao Zong, Garske Kristina M, Pan David Z, Koka Amogha, Kaminska Dorota, Männistö Ville, Sinsheimer Janet S, Pihlajamäki Jussi, Pajukanta Päivi

Publisher: Elsevier

Publication year: 2022

Journal: HGG advances

Journal name in source: HGG advances

Journal acronym: HGG Adv

Volume number: 3

Issue number: 1

eISSN: 2666-2477

DOI: http://dx.doi.org/10.1016/j.xhgg.2021.100056

URL: https://doi.org/10.1016/j.xhgg.2021.100056

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/174649675


Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD), now also known as metabolic dysfunction-associated fatty liver disease (MAFLD), is rapidly increasing worldwide due to the ongoing obesity epidemic. However, currently the NALFD diagnosis requires non-readily available imaging technologies or liver biopsy, which has drastically limited the sample sizes of NAFLD studies and hampered the discovery of its genetic component. Here we utilized the large UK Biobank (UKB) to accurately estimate the NAFLD status in UKB based on common serum traits and anthropometric measures. Scoring all individuals in UKB for NAFLD risk resulted in 28,396 NAFLD cases and 108,652 healthy individuals at a >90% confidence level. Using this imputed NAFLD status to perform the largest NAFLD genome-wide association study (GWAS) to date, we identified 94 independent (R2 < 0.2) NAFLD GWAS loci, of which 90 have not been identified before; built a polygenic risk score (PRS) model to predict the genetic risk of NAFLD; and used the GWAS variants of imputed NAFLD for a tissue-aware Mendelian randomization analysis that discovered a significant causal effect of NAFLD on coronary artery disease (CAD). In summary, we accurately estimated the NAFLD status in UKB using common serum traits and anthropometric measures, which empowered us to identify 90 GWAS NAFLD loci, build NAFLD PRS, and discover a significant causal effect of NAFLD on CAD.

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Last updated on 2022-11-08 at 15:14