Identification of Nine Novel Loci Associated with White Blood Cell Subtypes in a Japanese Population

White blood cells (WBCs) mediate immune systems and consist of various subtypes with distinct roles. Elucidation of the mechanism that regulates the counts of the WBC subtypes would provide useful insights into both the etiology of the immune system and disease pathogenesis. In this study, we report results of genome-wide association studies (GWAS) and a replication study for the counts of the 5 main WBC subtypes (neutrophils, lymphocytes, monocytes, basophils, and eosinophils) using 14,792 Japanese subjects enrolled in the BioBank Japan Project. We identified 12 significantly associated loci that satisfied the genome-wide significance threshold of P<5.0×10−8, of which 9 loci were novel (the CDK6 locus for the neutrophil count; the ITGA4, MLZE, STXBP6 loci, and the MHC region for the monocyte count; the SLC45A3-NUCKS1, GATA2, NAALAD2, ERG loci for the basophil count). We further evaluated associations in the identified loci using 15,600 subjects from Caucasian populations. These WBC subtype-related loci demonstrated a variety of patterns of pleiotropic associations within the WBC subtypes, or with total WBC count, platelet count, or red blood cell-related traits (n = 30,454), which suggests unique and common functional roles of these loci in the processes of hematopoiesis. This study should contribute to the understanding of the genetic backgrounds of the WBC subtypes and hematological traits

Video Supporting_file_01[1]

Video for CA was defined as positive when all of the following three criteria were met upon observation of the LES performed with the attached ST Hood short-type: a) Congestion inside the hood, b) ischemic change around the hood, and c) palisade vessels outside the hood

Data from: New endoscopic finding of esophageal achalasia with ST Hood short type: corona appearance

Background and Study Aims: Detecting esophageal achalasia remains a challenge. We describe the diagnostic utility of corona appearance, a novel endoscopic finding specific to esophageal achalasia. Patients and Methods: Corona appearance and seven conventional endoscopic findings were compared for sensitivity and consistency (-value) among 53 untreated esophageal achalasia patients who underwent endoscopy at our hospital. The following criteria had to be met during lower esophageal sphincter examination using the attached ST Hood short-type for positive corona appearance: A) congestion inside the hood, B) ischemic change around the hood, and C) palisade vessels outside the hood. Results: Corona appearance had the highest sensitivity (91%; -value, 0.71). Other findings in descending order of sensitivity included 1) functional stenosis of the esophagogastric junction (EGJ; 86%; -value, 0.58), 2) mucosal thickening and whitish change (71%; -value, 0.27), 3) abnormal contraction of the esophageal body (59%; -value, 0.32), 4) dilation of the esophageal lumen (58%; -value, 0.53), 5) liquid remnant (57%; -value, 0.51), 6) Wrapping around EGJ (49%; -value, 0.14), and 7) food remnant (30%; -value, 0.88). Even in 22 patients with poor (grade 1) intraluminal expansion, corona appearance had highest sensitivity (88%) compared to other endoscopic findings (-value, 0.63). Conclusions: Among endoscopic findings using a ST Hood short-type to diagnose esophageal achalasia, corona appearance had the highest sensitivity and its consistency (-value) among endoscopists was substantial compared to other endoscopic findings. Similar results were obtained for esophageal achalasia cases with poor expansion. Endoscopic diagnosis of esophageal achalasia with hood attached is useful

Sensitivity and κ-value of endoscopic findings in undilated achalasia (degree of dilation I).

<p>Sensitivity and κ-value of endoscopic findings in undilated achalasia (degree of dilation I).</p

Endoscopic findings of the LES with hood (right) and without hood (left).

<p>Endoscopic findings of the LES with hood (right) and without hood (left).</p

New endoscopic finding of esophageal achalasia with ST Hood short type: Corona appearance - Fig 2

<p>CA was defined as positive when all of the following three criteria were met upon observation of the LES performed with the attached ST Hood short-type: a) Congestion inside the hood, b) ischemic change around the hood, and c) palisade vessels outside the hood.</p

General sensitivity and κ-value of endoscopic findings in achalasia.

<p>General sensitivity and κ-value of endoscopic findings in achalasia.</p

General clinical features of patients with achalasia.

<p>General clinical features of patients with achalasia.</p

Endoscopic findings in esophageal achalasia.

<p>a: Functional stenosis of the esophagogastric junction. b: Wrapping around the esophagogastric junction. c: Abnormal contraction of the esophageal body. d: Mucosal thickening and whitish change. e: Dilation of the esophageal lumen. f, g: Liquid and/or food remnant.</p

Corona of the sun.

<p>Source of photo: Nisshoku no subete, chasing shadows, an observer’s guide to solar eclipses, Osamu Ohgoe, Kazuo Shiota, Seibundo Shinkosha Publishing Co., Ltd. Quoted by the permission of Seibundo Shinkosha Publishing Co., Ltd. and Kazuo Shiota provided permission to republish this image under the Creative Commons Attribution (CC BY) 4.0 license.</p