GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms

Lucas D. Ward (), Ho-Chou Tu, Chelsea B. Quenneville, Shira Tsour, Alexander O. Flynn-Carroll, Margaret M. Parker, Aimee M. Deaton, Patrick A. J. Haslett, Luca A. Lotta, Niek Verweij, Manuel A. R. Ferreira, Aris Baras, Gregory Hinkle and Paul Nioi
Additional contact information
Lucas D. Ward: Alnylam Pharmaceuticals
Ho-Chou Tu: Alnylam Pharmaceuticals
Chelsea B. Quenneville: Alnylam Pharmaceuticals
Shira Tsour: Alnylam Pharmaceuticals
Alexander O. Flynn-Carroll: Alnylam Pharmaceuticals
Margaret M. Parker: Alnylam Pharmaceuticals
Aimee M. Deaton: Alnylam Pharmaceuticals
Patrick A. J. Haslett: Alnylam Pharmaceuticals
Luca A. Lotta: Regeneron Genetics Center
Niek Verweij: Regeneron Genetics Center
Manuel A. R. Ferreira: Regeneron Genetics Center
Aris Baras: Regeneron Genetics Center
Gregory Hinkle: Alnylam Pharmaceuticals
Paul Nioi: Alnylam Pharmaceuticals

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Understanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities have proven useful for investigating liver biology. Here we report 100 loci associating with both enzymes, using GWAS across 411,048 subjects in the UK Biobank. The rare missense variant SLC30A10 Thr95Ile (rs188273166) associates with the largest elevation of both enzymes, and this association replicates in the DiscovEHR study. SLC30A10 excretes manganese from the liver to the bile duct, and rare homozygous loss of function causes the syndrome hypermanganesemia with dystonia-1 (HMNDYT1) which involves cirrhosis. Consistent with hematological symptoms of hypermanganesemia, SLC30A10 Thr95Ile carriers have increased hematocrit and risk of iron deficiency anemia. Carriers also have increased risk of extrahepatic bile duct cancer. These results suggest that genetic variation in SLC30A10 adversely affects more individuals than patients with diagnosed HMNDYT1.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24563-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24563-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24563-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().