Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis.
Nat Commun. 2015;6:6793
Authors: Zuo X, Sun L, Yin X, Gao J, Sheng Y, Xu J, Zhang J, He C, Qiu Y, Wen G, Tian H, Zheng X, Liu S, Wang W, Li W, Cheng Y, Liu L, Chang Y, Wang Z, Li Z, Li L, Wu J, Fang L, Shen C, Zhou F, Liang B, Chen G, Li H, Cui Y, Xu A, Yang X, Hao F, Xu L, Fan X, Li Y, Wu R, Wang X, Liu X, Zheng M, Song S, Ji B, Fang H, Yu J, Sun Y, Hui Y, Zhang F, Yang R, Yang S, Zhang X
Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 × 10(-08)). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D-LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.
PMID: 25854761 [PubMed - in process]
The obesity related FTO gene variant associates with the risk of recurrent miscarriage.
Acta Obstet Gynecol Scand. 2015 Apr 2;
Authors: Andraweera PH, Dekker GA, Jayasekara RW, Dissanayake VH, Roberts CT
OBJECTIVE: To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single nucleotide polymorphism (SNP) with recurrent miscarriage (RM).
DESIGN: Candidate gene association study.
SETTING: Human Genetics Unit, Colombo, Sri Lanka.
POPULATION: 202 Sinhalese women with two or more first trimester miscarriages and no living children (cases) and 202 age and ethnicity matched women with no history of miscarriage and having two or more living children (controls).
METHODS: Peripheral blood was collected from the participants and DNA was extracted. Genotyping was performed at the Australian genome Research Facility using the Sequenom MassARRAY system. Genotype and allele frequencies of cases were compared with controls using chi-squared testing.
MAIN OUTCOME MEASURES: The prevalence of the SNP in cases and controls.
RESULTS: The mean age of the women in the RM group was 31.9 ± 0.4 years and that of the control group was 32.3 ± 0.3 years. Of the women in the RM group, 140 (69.3%) had experienced ≥3 first trimester miscarriages. The prevalence of the AA genotype [p = 0.0002, OR (95% CI) = 3.8 (1.8-8.0)] and A allele [p = 0.002, OR (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 SNP were increased in women in the RM group compared to the control group.
CONCLUSION: The obesity related FTO rs9939609 SNP associates with RM. This finding warrants further investigation with controlling for important factors such as body mass index, diabetes and cardiovascular disease status. The SNP may be useful in predicting the risk of recurrent miscarriage. This article is protected by copyright. All rights reserved.
PMID: 25845303 [PubMed - as supplied by publisher]
A Common Variant Of Ubiquinol-Cytochrome c Reductase Complex Is Associated with DDH.
PLoS One. 2015;10(4):e0120212
Authors: Sun Y, Wang C, Hao Z, Dai J, Chen D, Xu Z, Shi D, Mao P, Teng H, Gao X, Hu Z, Shen H, Jiang Q
PURPOSE: Genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS) for DDH.
METHODS: We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide association study (GWAS). Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B).
RESULTS: In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7). In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338) with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.63*10-6 with the odds ratio of 1.35 (1.19-1.53) for allele A.
CONCLUSION: Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.
PMID: 25848760 [PubMed - in process]
A single nucleotide polymorphism in the MTOR gene is associated with recurrent spontaneous abortion in the Chinese female population.
Syst Biol Reprod Med. 2015 Apr 7;:1-6
Authors: Xiang H, Liu S, Zong C, Li Z, Liu Y, Ma X, Cao Y
Recurrent spontaneous abortion (RSA) is a multi-factor disease. The mammalian target of the the rapamycin (MTOR) gene has been reported to be involved in mouse embryo development and regulates the proliferation of embryonic stem cells. Our study explored the relationship between the single nucleotide polymorphism (SNP) rs17027478 in the promoter region of MTOR gene and the development of RSA. A total of 306 patients with RSA and 127 healthy females as the controls were recruited in the case-control study. The predesigned TaqMan SNP Genotyping Assay was adopted to analyze the association between rs17027478 and the development of RSA. Quantitative real-time reverse transcription polymerase chain reaction and luciferase reporter assays were conducted to analyze the function of the variant. It was found that a significant association exists between the variant and the risk of RSA among the patients who experienced no less than three spontaneous abortions (p = 0.043). However, the significant difference disappeared among the total samples (p = 0.524). Furthermore, we observed lower MTOR mRNA levels in the blood of RSA patients compared with healthy females (p = 0.020). The luciferase reporter assay showed that the rs17027478A allele significantly reduced the luciferase activity (p = 0.029). The results demonstrated that the variant rs17027478 in the promoter region of MTOR might be a good candidate responsible for the pathogenesis of RSA. Abbreviations RSA recurrent spontaneous abortion MTOR mammalian target of rapamycin SNP single nucleotide polymorphism qRT-PCR quantitative real-time polymerase chain reaction URSA unexplained recurrent spontaneous abortion mTORC1 mTOR complex 1 ESC embryonic stem cells HKE-293 human embryonic kidney 293 cells HWE Hardy-Weinberg equilibrium ANOVA one-way analysis of variance.
PMID: 25848831 [PubMed - as supplied by publisher]