Depressive symptoms are common among middle-aged and older adults.^1,2 China, like much of Asia, is experiencing an increase in older adults. The prevalence of depressive symptoms in older adults has become an increasingly important public health priority.^3-5 A national survey in China⁶ showed that approximately 30% of men and 43% of women aged 45 years and older experienced depressive symptoms. Epidemiological studies^7-9 have found that depressive symptoms are associated with a range of negative health outcomes, such as coronary heart diseases, stroke, and all-cause mortality.

Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27×10⁻⁹) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer. After analysing glycans attached to human immunoglobulin G in 4,095 individuals, we performed the first genome-wide association study (GWAS) of the glycome of an individual protein. Nine genetic loci were found to associate with glycans with genome-wide significance. Of these, four were enzymes that directly participate in IgG glycosylation, thus the observed associations were biologically founded. The remaining five genetic loci were not previously implicated in protein glycosylation, but the most of them have been reported to be relevant for autoimmune and inflammatory conditions and/or haematological cancers. A particularly interesting gene, IKZF1 was found to be associated with multiple IgG N-glycans. This gene has been implicated in numerous diseases, including systemic lupus erythematosus (SLE). We analysed N-glycans in 101 cases with SLE and 183 matched controls and demonstrated their substantial biomarker potential. Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. Our results may also provide an explanation for opposite effects of some genes in autoimmune diseases and haematological cancer.

Obstructive sleep apnea (OSA) is a sleep disorder characterized as complete or partial upper airflow cessation during sleep. Although it has been widely accepted that OSA is a risk factor for the development of hypertension, the studies focusing on this topic revealed inconsistent results. We aimed to clarify the association between OSA and hypertension, including essential and medication-resistant hypertension. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. PubMed and Embase databases were used for searching the relevant studies published up to December 31, 2016. A quantitative approach of meta-analysis was performed to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). Twenty-six studies with 51 623 participants (28 314 men, 23 309 women; mean age 51.8 years) met inclusion criteria and were included in this study. Among them, six studies showed a significant association between OSA and resistant hypertension (pooled OR = 2.842, 95% CI = 1.703-3.980, P < 0.05). Meanwhile, the combination of 20 original studies on the association of OSA with essential hypertension also presented significant results with the pooled ORs of 1.184 (95% CI = 1.093-1.274, P < 0.05) for mild OSA, 1.316 (95% CI = 1.197-1.433, P < 0.05) for moderate OSA and 1.561 (95% CI = 1.287-1.835, P < 0.05) for severe OSA. Our findings indicated that OSA is related to an increased risk of resistant hypertension. Mild, moderate and severe OSA are associated essential hypertension, as well a dose-response manner relationship is manifested. The associations are relatively stronger among Caucasians and male OSA patients.