Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity

Acceleration of the Deamination of Cytosine through Photo-Crosslinking

Herein, we report the major factor for deamination reaction rate acceleration, i.e., hydrophilicity, by using various 5-substituted target cytosines and by carrying out deamination at high temperatures. Through substitution of the groups at the 5′-position of the cytosine, the effect of hydrophilicity was understood. It was then used to compare the various modifications of the photo-cross-linkable moiety as well as the effect of the counter base of the cytosine to edit both DNA and RNA. Furthermore, we were able to achieve cytosine deamination at 37 °C with a half-life in the order of a few hours

Application of Mass Spectrometry for Determining the Geographic Production Area of Wagyu Beef

Japanese Black cattle (Japanese Wagyu) beef is attracting attention for its aroma and marbling, and its handling is increasing worldwide. Here, we focused on the origin discrimination of Wagyu beef and analyzed the nutritional components of Japanese Wagyu (produced in multiple prefectures of Japan), Hybrid Wagyu (a cross between Angus and Wagyu cattle born in Australia and transported to Japan), and Australian Wagyu beef using mass spectrometry (MS). Triple-quadrupole liquid chromatography–MS was used to clarify the molecular species of lipids in Wagyu beef. Fourteen classes of lipids were separated, and 128 different triacylglycerides (TGs) were detected. A simple comparative analysis of these TGs using high-performance liquid chromatography revealed significantly higher levels of triolein (C18:1/C18:1/C18:1; abbreviated OOO) and C18:1/C18:1/C16:1 (OOPo) in Japanese Wagyu. Wagyu elements beef were comprehensively analyzed using inductively coupled plasma (ICP)–MS and ICP–optical emission spectrometry. We found significant differences in the rubidium, cesium, and lithium levels of Japanese and Australian Wagyu beef. On comparing metabolites using gas chromatography–MS, we identified significant differences in the levels of amino acids and other components of the Japanese and Australian Wagyu beef. These results suggest the possibility of determining the origin of Wagyu cattle breeds using MS and genetic discrimination

Genome wide association study of HTLV-1–associated myelopathy/tropical spastic paraparesis in the Japanese population

International audienceHTLV-1–associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A , -B , -C , -DPB1 , -DQB1 , and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I ( P = 1.54 × 10 −9 ) and class II ( P = 1.21 × 10 −8 ) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C * 07:02 ( P = 2.61 × 10 −5 ), HLA-B * 07:02 ( P = 4.97 × 10 −10 ), HLA-DRB1 * 01:01 ( P = 1.15 × 10 −9 ) and HLA-DQB1 * 05:01 ( P = 2.30 × 10 −9 ) were associated with disease risk, while HLA-B * 40:06 ( P = 3.03 × 10 −5 ), HLA-DRB1 * 15:01 ( P = 1.06 × 10 −5 ) and HLA-DQB1 * 06:02 ( P = 1.78 × 10 −6 ) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP ( P = 9.52 × 10 −10 ); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P &lt; 5.0 × 10(-8)) and an additional 14 at P &lt; 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity