Variants of the low oxygen sensors EGLN1 and HIF-1AN associated with acute mountain sickness.

Two low oxygen sensors, Egl nine homolog 1 (EGLN1) and hypoxia-inducible factor 1-α inhibitor (HIF-1AN), play pivotal roles in the regulation of HIF-1α, and high altitude adaption may be involved in the pathology of acute mountain sickness (AMS). Here, we aimed to analyze single nucleotide polymorphisms (SNPs) in the untranslated regions of the EGLN1 and HIF-1AN genes and SNPs chosen from a genome-wide adaptation study of the Han Chinese population. To assess the association between EGLN1 and HIF-1AN SNPs and AMS in a Han Chinese population, a case-control study was performed including 190 patients and 190 controls. In total, thirteen SNPs were genotyped using the MassARRAY® MALDI-TOF system. Multiple genetic models were tested; The Akaike's information criterion (AIC) and Bayesian information criterion (BIC) values indicated that the dominant model may serve as the best-fit model for rs12406290 and rs2153364 of significant difference. However, these data were not significant after Bonferroni correction. No significant association was noted between AMS and rs12757362, rs1339894, rs1361384, rs2009873, rs2739513 or rs2486729 before and after Bonferroni correction. Further haplotype analyses indicated the presence of two blocks in EGLN1; one block consists of rs12406290-rs2153364, located upstream of the EGLN1 gene. Carriers of the "GG" haplotype of rs12406290-rs2153364 exhibited an increased risk of AMS after adjustments for age and smoking status. However, no significant association was observed among HIF-1AN 3'-untranslated region (3'-UTR) polymorphisms, haplotype and AMS. Our study indicates that variants in the EGLN1 5'-UTR influence the susceptibility to AMS in a Han Chinese population

Ancestry Informative Marker Set for Han Chinese Population

The population of Han Chinese is ∼1.226 billion people. Genetic heterogeneity between northern Han Chinese (N-Han) and southern Han Chinese (S-Han) has been demonstrated by recent genome-wide studies. As an initial step toward health disparities and personalized medicine in Chinese population, this study developed a set of ancestry informative markers (AIM) for Han Chinese population

Association between the G-protein β3 subunit C825T polymorphism with essential hypertension: a meta-analysis in Han Chinese population

We aimed to evaluate the contribution of the G-protein β3 subunit C825T (GNB3-C825T) polymorphism to essential hypertension (EH) in Han Chinese population by performing meta-analysis. A meta-analysis was performed in 12 case–control genetic association studies including 3,020 hypertension patients and 2,790 controls from MEDLINE (PubMed) and the China National Knowledge Infrastructure platforms. The STATA 10.0 software was used in analysis. Overall, there was no significant association between the GNB3-C825T polymorphism and EH in neither additive [TT vs. CC: OR (95 % CI) = 1.11 (0.74–1.69), P = 0.61; TC vs. CC: OR (95 % CI) = 1.08 (0.89–1.31), P = 0.42], nor dominant [TT + TC vs. CC: OR (95 % CI) = 1.11 (0.86–1.42), P = 0.43] and nor recessive [TT vs. TC + CC: OR (95 % CI) = 1.04 (0.75–1.44), P = 0.81] genetic models. Although further subgroup analysis found statistically significant results [T vs. C: OR (95 % CI) = 1.50 (1.05–2.15), P = 0.03] in the southern population, but after exclusion one particular study, the significant association was disappeared. No significant result was found in the northern Han Chinese population. There was no significant association identified between GNB3-C825T polymorphism and EH in Han Chinese population. Further larger sample and well-designed studies are needed to assess the genetic association particularly in the southern Han Chinese population

New insights from GWAS for the cleft palate among han Chinese population

Genome wide association studies (GWAS) already have identified tens of susceptible loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, whether these loci associated with nonsyndromic cleft palate only (NSCPO) remains unknown. In this study, we replicated 38 SNPs (Single nucleotide polymorphisms) which has the most significant p values in published GWASs, genotyping by using SNPscan among 144 NSCPO trios from Western Han Chinese. We performed the transmission disequilibrium test (TDT) on individual SNPs and gene-gene (GxG) interaction analyses on the family data; Parent-of-Origin effects were assessed by separately considering transmissions from heterozygous fathers versus heterozygous mothers to affected offspring. Allelic TDT results showed that T allele at rs742071 (PAX7) (p=0.025, ORtransmission=3.00, 95%CI: 1.09-8.25) and G allele at rs2485893 (10kb 3? of SYT14) were associated with NSCPO (p=0.0036, ORtransmission= 0.60, 95%CI: 0.42-0.85). Genotypic TDT based on 3 pseudo controls further confirmed that rs742071 (p-value=0.03, ORtransmission=3.00, 95%CI: 1.09-8.25) and rs2485893 were associated with NSCPO under additive model (p-value= 0.02, ORtransmission= 0.66, 95%CI: 0.47-0.92). Genotypic TDT for epistatic interactions showed that rs4844913 (37kb 3? of DIEXF) interacted with rs11119388 (SYT14) (p-value=1.80E-08) and rs6072081 (53kb 3? of MAFB) interacted with rs6102085 (33kb 3? of MAFB) (p-value=3.60E-04) for NSCPO, suggesting they may act in the same pathway in the etiology of NSCPO. In this study, we found that rs742071 and rs2485893 were associated NSCPO from Han Chinese population; also, interactions of rs4844913:rs11119388 and rs6072081:rs6102085 for NSCPO were identified, gene-gene interactions have been proposed as a potential source of the remaining heritability, these findings provided new insights of the previous GWAS

Susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population

<p>Abstract</p> <p>Background</p> <p>Several linkage studies across multiple population groups provide convergent support for susceptibility loci for schizophrenia – and, more recently, for affective disorder – on chromosome 6q. We explore whether schizophrenia and affective disorder have common susceptibility gene on 6q in Han Chinese population.</p> <p>Methods</p> <p>In the present study, we genotyped 45 family trios from Han Chinese population with mixed family history of schizophrenia and affective disorder. Twelve short tandem repeat (STRs) markers were selected, which covered 102.19 cM on chromosome 6q with average spacing 9.29 cM and heterozygosity 0.78. The transmission disequilibrium test (TDT) was performed to search for susceptibility loci to schizophrenia and affective disorder.</p> <p>Results</p> <p>The results showed STRs D6S257, D6S460, D6S1021, D6S292 and D6S1581 were associated with susceptibility to psychotic disorders. When families were grouped into schizophrenia and affective disorder group, D6S257, D6S460 and D6S1021, which map closely to the centromere of chromosome 6q, were associated with susceptibility to schizophrenia. Meanwhile, D6S1581, which maps closely to the telomere, was associated with susceptibility to affective disorder. But after correction of multiple test, all above association were changed into no significance (P > 0.05).</p> <p>Conclusion</p> <p>These results suggest that susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population.</p

Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population

Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data

Association of DTNBP1 With Schizophrenia: Findings From Two Independent Samples of Han Chinese Population

Objectives: Schizophrenia (SZ) is a complex psychiatric disorder that has a strong genetic basis. Dystrobrevin-binding protein 1 (DTNBP1) is one of the genes thought to be pivotal in regulating the glutamatergic system. Studies have suggested that variations in DTNBP1 confer susceptibility to SZ and clinical symptoms. Here, we performed a two-stage independent verification study to identify polymorphisms of the DTNBP1 gene that might be associated with SZ in the Han Chinese population. Methods: In stage 1, 14 single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 healthy controls (HCs) using the Illumina GoldenGate assays on a BeadStation 500G Genotyping System. In stage 2, ten SNPs were genotyped in an independent sample of 1,031 SZ patients and 621 HCs using the Illumina 660k Genotyping System. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale. Results: There was a significant association related to allele frequency, and a trend association in relation to genotype between SZ patients and HCs at rs4712253 (p = 0.03 and 0.05, respectively). These associations were not evident following Bonferroni correction (p \u3e 0.05 for both). Haplotype association analysis revealed that only two haplotypes (GAG and GAA; rs16876575-rs9464793-rs4712253) were significantly different between SZ patients and HCs (chi(2) = 4.24, 6.37, p = 0.04 and 0.01, respectively). In addition, in SZ patients there was a significant association in the rs4964793 genotype for positive symptoms, and in the rs1011313 genotype for excitement/hostility symptoms (p = 0.01 and 0.002, respectively). We found a significant association in the baseline symbol digital modalities test (SDMT), forward-digital span (DS), backward-DS, and semantic fluency between SZ patients and HCs (p \u3c 0.05 for all). Finally, the SNP rs1011313 genotypes were associated with SDMT in SZ patients (p = 0.04). Conclusion: This study provides further evidence that SNP rs4712253 of DTNBP1 has a nominal association with SZ in the Han Chinese population. Such a genotype variation may play a role in psychopathology and cognitive function