TY - JOUR
T1 - Replication of fifteen loci involved in human plasma protein N-glycosylation in 4,802 samples from four cohorts
AU - Sharapov, Sodbo Zh
AU - Shadrina, Alexandra S
AU - Tsepilov, Yakov A
AU - Elgaeva, Elizaveta E
AU - Tiys, Evgeny S
AU - Feoktistova, Sofya G
AU - Zaytseva, Olga O
AU - Vuckovic, Frano
AU - Cuadrat, Rafael
AU - Jäger, Susanne
AU - Wittenbecher, Clemens
AU - Karssen, Lennart C
AU - Timofeeva, Maria
AU - Tillin, Therese
AU - Trbojević-Akmačić, Irena
AU - Štambuk, Tamara
AU - Rudman, Najda
AU - Krištić, Jasminka
AU - Šimunović, Jelena
AU - Momčilović, Ana
AU - Vilaj, Marija
AU - Jurić, Julija
AU - Slana, Anita
AU - Gudelj, Ivan
AU - Klarić, Thomas
AU - Puljak, Livia
AU - Skelin, Andrea
AU - Jeličić Kadić, Antonia
AU - Van Zundert, Jan
AU - Chaturvedi, Nishi
AU - Campbell, Harry
AU - Dunlop, Malcolm
AU - Farrington, Susan M
AU - Doherty, Margaret
AU - Dagostino, Concetta
AU - Gieger, Christian
AU - Allegri, Massimo
AU - Williams, Frances
AU - Schulze, Matthias B
AU - Lauc, Gordan
AU - Aulchenko, Yurii S
N1 - © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2020/6/10
Y1 - 2020/6/10
N2 - 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 (4,802 individuals) to replicate the previously identified loci. For all but one locus, the expected replication power exceeded 95%. Of the sixteen loci reported previously, fifteen 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 fifteen replicated loci present a good target for further functional studies. Among these, eight genes encode 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.
AB - 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 (4,802 individuals) to replicate the previously identified loci. For all but one locus, the expected replication power exceeded 95%. Of the sixteen loci reported previously, fifteen 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 fifteen replicated loci present a good target for further functional studies. Among these, eight genes encode 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.
U2 - 10.1093/glycob/cwaa053
DO - 10.1093/glycob/cwaa053
M3 - Article
C2 - 32521004
JO - Glycobiology
JF - Glycobiology
SN - 0959-6658
ER -