Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Seizures in Chinese Patients with Myelin Oligodendrocyte Glycoprotein Encephalomyelitis: A retrospective study in single center

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody associated encephalomyelitis is increasingly being considered a distinct disease entity, with seizure and encephalopathy commonly reported. Object: To investigate the clinical features of MOG-IgG positive patients with seizures and /or encephalopathy in a single cohort. Methods: Overall, 58 patients seropositive for MOG-IgG, including 23 paitents with seizures and/or encephalopathy and 35 patients without seizures or encephalopathy were included. Results: The incidence of seizures and/or encephalopathy was 39.66% (23/58). Either at disease onset or throughout the course of disease, meningeal irritation (P=0.030, P=0.011), fever (P=0.001, P=0.000), headache (P=0.001, P=0.000), nausea and vomiting (P=0.004, P=0.000) were significantly higher in patients with seizures and/or encephalopathy than the control group. There was less optic nerve (P=0.003) and spinal cord (P=0.037) involvement in the patients with seizures and/or encephalopathy. CSF leukocytes were elevated in both seizures and/or encephalopathy group and the control group. Most of MOG encephalomyelitis patients had cortical/subcortical lesions, including 65.2%(15/23) in the seizures and/or encephalopathy group and 50.0%(13/26) in the control group. Subgroup analysis showed that 30%(7/23) MOG-IgG positive subjects with seizures and/or encephalopathy had been misdiagnosed for central nervous system infection due to meningoencephalitis symptom and elevated CSF leukocytes (P=0.002). Conclusions: Seizures and encephalopathy are not rare in MOG encephalomyelitis, which may be associated with cortical/subcortical brain lesion. MOG encephalomyelitis patients often combined meningoencephalitis symptom and abnormal CSF presentation, mimic CNS infection

Ectrodactyly in A Chinese Patient Born to A Mother with Neuromyelitis Optica Spectrum Disorder

Background: NMOSD develops primarily in women of childbearing age, and several previous studies have shown that the disorder may increase the risk of miscarriage. Objective: To report a case of fetal malformation related to NMOSD. Methods: We studied the case history a 30-year-old woman who was diagnosed with NMOSD who gave birth to an infant with ectrodactyly and the pathological manifestation of her placenta. Results: The patient experienced recurrent neuritis and who was seropositive for AQP4-IgG. She became pregnant, and the fetus was found to have ectrodactyly. Histological analysis of the placenta showed moderate inflammatory infiltration. Conclusion: It is important to be aware of NMOSD-related fetal malformation. Whether fetal malformation in NMOSD is related to inflammation and AQP4-IgG remains to be determined