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Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts.

ABSTRACT: Human protein glycosylation is a complex process, and its in vivo regulation is poorly understood. Changes in glycosylation patterns are associated with many human diseases and conditions. Understanding the biological determinants of protein glycome provides a basis for future diagnostic and therapeutic applications. Genome-wide association studies (GWAS) allow to study biology via a hypothesis-free search of loci and genetic variants associated with a trait of interest. Sixteen loci were identified by three previous GWAS of human plasma proteome N-glycosylation. However, the possibility that some of these loci are false positives needs to be eliminated by replication studies, which have been limited so far. Here, we use the largest set of samples so far (4802 individuals) to replicate the previously identified loci. For all but one locus, the expected replication power exceeded 95%. Of the 16 loci reported previously, 15 were replicated in our study. For the remaining locus (near the KREMEN1 gene), the replication power was low, and hence, replication results were inconclusive. The very high replication rate highlights the general robustness of the GWAS findings as well as the high standards adopted by the community that studies genetic regulation of protein glycosylation. The 15 replicated loci present a good target for further functional studies. Among these, eight loci contain genes encoding glycosyltransferases: MGAT5, B3GAT1, FUT8, FUT6, ST6GAL1, B4GALT1, ST3GAL4 and MGAT3. The remaining seven loci offer starting points for further functional follow-up investigation into molecules and mechanisms that regulate human protein N-glycosylation in vivo.

SUBMITTER: Sharapov SZ

PROVIDER: S-EPMC7874387 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts.

Sharapov Sodbo Zh SZ Shadrina Alexandra S AS Tsepilov Yakov A YA Elgaeva Elizaveta E EE Tiys Evgeny S ES Feoktistova Sofya G SG Zaytseva Olga O OO Vuckovic Frano F Cuadrat Rafael R Jäger Susanne S Wittenbecher Clemens C Karssen Lennart C LC Timofeeva Maria M Tillin Therese T Trbojević-Akmačić Irena I Štambuk Tamara T Rudman Najda N Krištić Jasminka J Šimunović Jelena J Momčilović Ana A Vilaj Marija M Jurić Julija J Slana Anita A Gudelj Ivan I Klarić Thomas T Puljak Livia L Skelin Andrea A Kadić Antonia Jeličić AJ Van Zundert Jan J Chaturvedi Nishi N Campbell Harry H Dunlop Malcolm M Farrington Susan M SM Doherty Margaret M Dagostino Concetta C Gieger Christian C Allegri Massimo M Williams Frances F Schulze Matthias B MB Lauc Gordan G Aulchenko Yurii S YS

Glycobiology 20210201 2

Human protein glycosylation is a complex process, and its in vivo regulation is poorly understood. Changes in glycosylation patterns are associated with many human diseases and conditions. Understanding the biological determinants of protein glycome provides a basis for future diagnostic and therapeutic applications. Genome-wide association studies (GWAS) allow to study biology via a hypothesis-free search of loci and genetic variants associated with a trait of interest. Sixteen loci were identi ...[more]

PMID: 32521004

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Dataset Information

Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts.

Publications

Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts.

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