Asset Details

MbrlCatalogueTitleDetail

Do you wish to reserve the book?

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

by Hinkle, Gregory , Flynn-Carroll, Alexander O , Verweij, Niek , Ward, Lucas D , Quenneville, Chelsea B , Baras, Aris , Center, Regeneron Genetics , Ho-Chou, Tu , Nioi, Paul , Geisinger-Regeneron Discovehr Collaboration , Deaton, Aimee M , Lotta, Luca A , Tsour, Shira , Ferreira, Manuel A R , Haslett, Patrick A J , Parker, Margaret M

in Alanine / Alanine transaminase / Aspartate aminotransferase / Bile ducts / Biobanks / Cholangiocarcinoma / Dystonia / Enzymes / Genetics / Genome-wide association studies / Genomes / Liver / Liver diseases / Manganese / Minority & ethnic groups

2021

Yes Please

Hey, we have placed the reservation for you!

By the way, why not check out events that you can attend while you pick your title.

Oops! Something went wrong.

Looks like we were not able to place the reservation. Kindly try again later.

Are you sure you want to remove the book from the shelf?

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

2021

Confirm

Do you wish to request the book?

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

2021

Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy

How would you like to get it?

Submit

We have requested the book for you!

Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.

Oops! Something went wrong.

Looks like we were not able to place your request. Kindly try again later.

Paper

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

Hinkle, Gregory,

Flynn-Carroll, Alexander O,

Verweij, Niek,

Ward, Lucas D,

Quenneville, Chelsea B,

Baras, Aris,

Center, Regeneron Genetics,

Ho-Chou, Tu,

Nioi, Paul,

Geisinger-Regeneron Discovehr Collaboration,

Deaton, Aimee M,

Lotta, Luca A,

Tsour, Shira,

Ferreira, Manuel A R,

Haslett, Patrick A J,

Parker, Margaret M

2021

Overview

Abstract To investigate mechanisms of hepatocellular damage, we performed genome-wide association studies (GWAS) on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities across 411,048 subjects from four ancestry groups in the UK Biobank, and found 100 loci associating with both enzymes. The rare missense variant SLC30A10 Thr95Ile (rs188273166) associates with a larger elevation in ALT and AST than any other variant tested and this association also 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 associations suggest that genetic variation in SLC30A10 adversely affects more individuals than patients with diagnosed HMNDYT1. Competing Interest Statement A.D., A.F.C., S.T., L.W., M.P., P.N., C.Q., H.C.T., G.H., and P.H. are employees of Alnylam Pharmaceuticals, Inc. L.L., N.V., M.F., and A.B. are employees of Regeneron Pharmaceuticals, Inc.

Share this book

Add to My Shelf

Publisher

Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory

Subject

Alanine

/ Alanine transaminase

/ Aspartate aminotransferase