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HPLC analysis of N-glycans quantified levels of the biantennary glycan (A2) in plasma proteins of 924 individuals. Subsequent genome-wide association study (GWAS) using 317,503 single nucleotide polymorphysms (SNP) identified two genetic loci influencing variation in A2: FUT 8 and ESR2. We demonstrate that human glycans are amenable to GWAS and their genetic regulation shows sex-specific effects with FUT 8 variants explaining 17.3% of the variance in pre-menopausal women, while ESR2 variants explained 6.0% of the variance in post-menopausal women.

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Genome-wide association study identifies FUT8 and ESR2 as co-regulators of a bi-antennary N-linked glycan A2 (GlcNAc~2~Man~3~GlcNAc~2~) in human plasma proteins