Genome-Wide Association Study of Young-Onset Hypertension in the Han Chinese Population of Taiwan

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (−log10(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (−log10(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Electrical and Hysteresis Characteristics of Top-Gate InGaZnO Thin-Film Transistors with Oxygen Plasma Treatment Prior to TEOS Oxide Gate Dielectrics

We report the impact of oxygen (O2) plasma time on an amorphous indium–gallium–zinc oxide (a-IGZO) thin-film surface that was carried out before TEOS deposition in order to optimize the performance of thin-film transistors (TFTs). TheO2 plasma time of 60 s possessed the largest on/off current ratio of >108, with a field-effect mobility (µFE) of 8.14 cm2 V−1 s−1, and the lowest subthreshold swing (S.S.) of 0.395 V/decade, with a threshold voltage (Vth) of −0.14 V. However, increases in Ioff and S.S. and decreases in the µFE were observed for the longer O2 plasma time of 120 s. As the O2 plasma time increased, the reduction in the carrier concentration in the IGZO channel layer may have resulted in an increase in Vth for the IGZO TFT devices. With an increase in the O2 plasma time, the surface roughness of the IGZO channel layer was increased, the carbon content in the TEOS oxide film was reduced, and the film stoichiometry was improved. The SIMS depth profile results showed that the O/Si ratio of TEOS oxide for the sample with the O2 plasma time of 60 s was 2.64, and its IGZO TFT device had the best electrical characteristics. In addition, in comparison to the IGZO TFT device without O2 annealing, larger clockwise hysteresis in the transfer characteristics revealed that a greater number of electrons were trapped at the interface between TEOS oxide and the a-IGZO channel layer. However, hysteresis curves of the O2-annealed IGZO TFTs with various O2 plasma times were greatly reduced, meaning that the electron traps were reduced by O2 annealing

Electrical Characteristics and Stability Improvement of Top-Gate In-Ga-Zn-O Thin-Film Transistors with Al2O3/TEOS Oxide Gate Dielectrics

In this work, two stacked gate dielectrics of Al2O3/tetraethyl-orthosilicate (TEOS) oxide were deposited by using the equivalent capacitance with 100-nm thick TEOS oxide on the patterned InGaZnO layers to evaluate the electrical characteristics and stability improvement of amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) devices, including positive bias stress (PBS) and negative bias stress (NBS) tests. Three different kinds of gate dielectrics (Al2O3, TEOS, Al2O3/TEOS) were used to fabricate four types of devices, differing by the gate dielectric, as well as its thickness. As the Al2O3 thickness of Al2O3/TEOS oxide dielectric stacks increased, both the on-current and off-current decreased, and the transfer curves shifted to larger voltages. The lowest ∆Vth of 0.68 V and ∆S.S. of −0.03 V/decade from hysteresis characteristics indicate that the increase of interface traps and charge trapping between the IGZO channel and gate dielectrics is effectively inhibited by using two stacked dielectrics with 10-nm thick Al2O3 and 96-nm thick TEOS oxide. The lowest ∆Vth and ∆S.S. values of a-IGZO TFTs with 10-nm thick Al2O3 and 96-nm thick TEOS oxide gate dielectrics according to the PBS and NBS tests were shown to have the best electrical stability in comparison to those with the Al2O3 or TEOS oxide single-layer dielectrics