TY - JOUR
T1 - Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 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 - Kadić, Antonia Jeličić
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 - Publisher Copyright:
© 2020 The Author(s).
PY - 2021/2/1
Y1 - 2021/2/1
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 (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.
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 (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.
KW - genetic association study
KW - glycosylation
KW - locus
KW - replication
KW - total plasma N-glycome
UR - http://www.scopus.com/inward/record.url?scp=85102095032&partnerID=8YFLogxK
U2 - 10.1093/glycob/cwaa053
DO - 10.1093/glycob/cwaa053
M3 - Article
C2 - 32521004
AN - SCOPUS:85102095032
SN - 0959-6658
VL - 31
SP - 82
EP - 88
JO - Glycobiology
JF - Glycobiology
IS - 2
ER -