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Abstract
Soybean is increasingly becoming one of the main oilseeds crops in Kazakhstan, with a major growing area in the south-eastern part of the country. The comparative assessment of small-size (108) and medium-size (276 accessions) collections of soybean originated from five regions of the world was made in field trials in Almaty region (south-east of Kazakhstan). The full collection was genotyped using the Illumina iSelect 6K SNP (single nucleotide polymorphism) array that allowed observation of 4651 polymorphic SNPs. The genome-wide association study (GWAS) was conducted using the following six important agronomic traits: flowering time, seed maturation time, plant height, number of fertile nodes, number of seeds per node, and thousand seed weight. In total, GWAS using TASSEL package identified 56 stable QTNs (quantitative trait nucleotdies) for all the studied traits, including 42 QTNs detected using the medium-size collection. It was shown that the medium-size population, in comparison with the small-size population, was preferable for the detection of significant associations. A comparative analysis of the data with previously published results suggested that 36 of the stable 56 QTNs were presumably novel associations. The revealed QTNs can be used in the molecular breeding projects for soybean yield improvement.

OBJECTIVE: To use high-resolution metabolomics (HRM) to identify metabolic changes in military personnel associated with deployment to Balad, Iraq, or Bagram, Afghanistan. METHODS: Pre- and post-deployment samples were obtained from the Department of Defense Serum Repository (DoDSR). HRM and bioinformatics were used to identify metabolic differences associated with deployment. RESULTS: Differences at baseline (pre-deployment) between personnel deployed to Bagram compared to Balad or Controls included sex hormone and keratan sulfate metabolism. Deployment to Balad was associated with alterations to amino acid and lipid metabolism, consistent with inflammation and oxidative stress, and pathways linked to metabolic adaptation and repair. Difference associated with deployment to Bagram included lipid pathways linked to cell signaling and inflammation. CONCLUSIONS: Metabolic variations in pre- and post-deployment are consistent with deployment-associated responses to air pollution and other environmental stressors.

Mexican Americans (MAs) and American Indians (AIs) constitute conspicuously understudied groups with respect to risk for post-traumatic stress disorder (PTSD), especially in light of findings showing racial/ethnic differences in trauma exposure and risk for PTSD. The purpose of this study was to examine genetic influences on PTSD in two minority cohorts. A genome-wide association study (GWAS) with sum PTSD symptoms for trauma-exposed subjects was run in each cohort. Six highly correlated variants in olfactory receptor family 11 subfamily L member 1 (OR11L1) were suggestively associated with PTSD in the MA cohort. These associations remained suggestively significant after permutation testing. A signal in a nearby olfactory receptor on chromosome 1, olfactory receptor family 2 subfamily L member 13 (OR2L13), tagged by rs151319968, was nominally associated with PTSD in the AI sample. Although no variants were significantly associated after correction for multiple testing in a meta-analysis of the two cohorts, pathway analysis of the top hits showed an enrichment cluster of terms related to sensory transduction, olfactory receptor activity, G-protein coupled receptors, and membrane. As previous studies have proposed a role for olfaction in PTSD, our results indicate this influence may be partially driven by genetic variation in the olfactory system.

Ye-Jin Lee,1 SeungHo Choi,2 Sung-Youn Kwon,2 Yunhwan Lee,2 Jung Kyu Lee,3 Eun Young Heo,3 Hee Soon Chung,3,4 Deog Kyeom Kim3,4 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 2Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 135-984 Korea; 3Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea; 4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, KoreaCorrespondence: Deog Kyeom KimDivision of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Boramae-Gil 41, Dongjak-gu, Seoul 156-707, Republic of KoreaTel +82-2-870-3207Fax +82-2-831-0714Email kimdkmd@gmail.comBackground: Identifying the genetic basis of airflow limitation is one of the most interesting issues for understanding chronic obstructive pulmonary disease (COPD) pathophysiology. Several studies have shown that some genetic variants associated with COPD have been identified in genome-wide association study (GWAS), especially in patients with moderate to severe COPD; genetic susceptibility for airflow limitation in the early COPD phase has not been widely studied.Objective: We investigated the genetic variants in early COPD.Methods: The present study analyzed Gene-environment interaction and phenotype (GENIE) cohort that included participants who received health screening examination. The association between single nucleotide polymorphism (SNP) and susceptibility to early COPD (FEV1 predicted ≥ 50% and FEV1/FVC < 0.7) was tested.Results: A total of 130 patients with early COPD and 3478 controls (1700 ever smokers and 1778 never smokers) were recruited. When compared with the total controls, certain SNPs (rs2818103, rs875033, rs9354627, rs34552148) on chromosome 6 were included at the top of our list (p= 5.6 × 10– 7 ∼ 9.6 × 10– 6) although they did not reach genome-wide significance. When compared with the never smoker controls, two SNPs (rs2857210, rs2621419) of the HLA-DQB2 gene class were persistently associated with susceptibility to early COPD.Conclusion: Certain SNPs located on chromosome 6 or the HLA-DQB2 gene were the top-scoring SNPs for the association with susceptibility to early COPD in the Korean GENIE cohort.Keywords: early chronic obstructive pulmonary disease, genome-wide association study, single nucleotide polymorphism, SNP, HLA-DQ gene

AbstractHuman height and body mass index are influenced by a large number of genes, each with small effects, along with environment. To identify common genetic variants associated with these traits, we performed genome-wide association studies in 11,536 individuals composed of Australian twins, family members, and unrelated individuals at ∼550,000 genotyped SNPs. We identified a single genome-wide significant variant for height (Pvalue = 1.06 × 10–9) located inHHIP, a well-replicated height-associated gene. Suggestive levels of association were found for other known genes associated with height (Pvalues < 1 × 10–6):ADAMTSL3,EFEMP1,GPR126, andHMGA2; and BMI (Pvalues < 1 × 10–4):FTOandMC4R. Together, these variants explain less than 2% of total phenotypic variation for height and 0.5% for BMI.

Background: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. Methods: We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. Results: We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10? 8): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10? 6), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10? 5), interleukin-4 signaling (p = 3.97 × 10? 5) and cell surface interactions at the vascular wall (p = 4.63 × 10? 5). Conclusions: Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci. ; This study was funded by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). This work has been also sponsored by the grant SEV-2011-00067 of Severo Ochoa Program, awarded by the Spanish Government. This work was supported by an EFSD/Lilly research fellowship. Josep M. Mercader was supported by Sara Borrell Fellowship from the Instituto Carlos III. Sílvia Bonàs was awarded an FI-DGR Fellowship from FI-DGR 2013 from Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya). The study sponsors had no role in the design of the study, collection, analysis or interpretation of the data.

Genome-wide association studies (GWAS) of attention-deficit/hyperactivity disorder (ADHD) offer the benefit of a hypothesis-free approach to measuring the quantitative effect of genetic variants on affection status. Generally the findings of GWAS relying on ADHD status have been non-significant, but the one study using quantitative measures of symptoms found SLC9A9 and SLC6A1 were associated with inattention and hyperactivity–impulsivity. Accordingly, we performed a GWAS using quantitative measures of each ADHD subtype measured with the Strengths and Weaknesses of ADHD and Normal Behaviour (SWAN) scale in two community-based samples. This scale captures the full range of attention and kinetic behavior; from high levels of attention and appropriate activity to the inattention and hyperactivity–impulsivity associated with ADHD within two community-based samples. Our discovery sample comprised 1,851 participants (mean age = 22.8 years [4.8]; 50.6% female), while our replication sample comprised 155 participants (mean age = 26.3 years [3.1]; 68.4% females). Age, sex, age × sex, and age2 were included as covariates and the results from each sample were combined using meta-analysis, then analyzed with a gene-based test to estimate the combined effect of markers within genes. We compare our results with markers that have previously been found to have a strong association with ADHD symptoms. Neither the GWAS nor subsequent meta-analyses yielded genome-wide significant results; the strongest effect was observed at rs2110267 (4.62 × 10−7) for symptoms of hyperactivity–impulsivity. The strongest effect in the gene-based test was for GPR139 on symptoms of inattention (6.40 × 10−5). Replication of this study with larger samples will add to our understanding of the genetic etiology of ADHD.

This work was supported by the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme (WCRF 2014/1180 to Konstantinos K Tsilidis). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF),Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford) (UK). ; Heath, A.K., Muller, D.C., Van Den Brandt, P.A., Papadimitriou, N., Critselis, E., Gunter, M., Vineis, P., Weiderpass, E., Fagherazzi, G., Boeing, H., Ferrari, P., Olsen, A., Tjønneland, A., Arveux, P., Boutron-Ruault, M.-C., Mancini, F.R., Kühn, T., Turzanski-Fortner, R., Schulze, M.B., Karakatsani, A., Thriskos, P., Trichopoulou, A., Masala, G., Contiero, P., Ricceri, F., ...

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field ; We report a prostate cancer genome-wide association follow-on study. We discovered four variants associated with susceptibility to prostate cancer in several European populations: rs10934853[A] (OR = 1.12, P = 2.9 x 10(-10)) on 3q21.3; two moderately correlated (r2 = 0.07) variants, rs16902094[G] (OR = 1.21, P = 6.2 x 10(-15)) and rs445114[T] (OR = 1.14, P = 4.7 x 10(-10)), on 8q24.21; and rs8102476[C] (OR = 1.12, P = 1.6 x 10(-11)) on 19q13.2. We also refined a previous association signal on 11q13 with the SNP rs11228565[A] (OR = 1.23, P = 6.7 x 10(-12)). In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, we estimated that carriers in the top 1.3% of the risk distribution are at a 2.5 times greater risk of developing the disease than members of the general population. ; info:eu-repo/grantAgreement/EC/FP7/218071 European Union 202059 V Foundation US Department of Veterans Affairs Academy of Finland Sigrid Juselius Foundation Pirkanmaa Hospital District, Tampere University Hospital

Death by suicide and suicidal behavior are major concerns among U.S. military veterans; however, no genome-wide association studies (GWAS) studies of suicidal behavior have been conducted among U.S. military veterans to date, despite the elevated rate of suicidal behavior observed within this population. Accordingly, the primary objective of the present research was to conduct the first GWAS of suicide attempts and suicidal ideation in a large and well-characterized sample of U.S. military veterans. The gene most significantly associated (p=9.28×10(−7)) with suicide attempts was the Potassium Calcium-Activated Channel Subfamily M Regulatory Beta Subunit 2 (KCNMB2) gene, which plays a key role in neuronal excitability. In addition, replication analyses provided additional support for the potential role of the ABI Family Member 3 Binding Protein (ABI3BP) gene in the pathogenesis of suicidal behavior, as numerous nominal associations were found between this gene and both suicide attempts and suicidal ideation. Additional work aimed at replicating and extending these findings is needed.

Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10-8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10-17), 6q23.3 (rs6928977, P = 4.62 × 10-11), 10p14 (rs3781093, P = 9.49 × 10-13), 13q34 (rs112998813, P = 4.58 × 10-8) and 16p13.13 (rs34972832, P = 2.12 × 10-8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response. ; In the United Kingdom, Bloodwise (LLR; 10021) provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the Lymphoma Research Trust is also acknowledged. A.S. is supported by a clinical fellowship from Cancer Research UK. For the UK-GWAS, sample and data acquisition were supported by Breast Cancer Now, the European Union and the Lymphoma Research Trust. The UK-GWAS made use of control genotyping data generated by the WTCCC. We acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, which was funded by the Medical Research Council Grant G0000934 and the Wellcome Trust Grant 068545/Z/02. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk. Funding for this project was provided by the Wellcome Trust under awards 076113 and 085475. Patients for the new GWAS were ascertained through the National Study of Hodgkin Lymphoma Genetics (http://www.public.ukcrn.org.uk) and we thank the HighThroughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z) for the generation of Genotyping data. The BCAC study would not have been possible without the contributions of the following: Manjeet K. Bolla, Qin Wang, Kyriaki Michailidou and Joe Dennis. BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A16563). For the BBCS study, we thank Eileen Williams, Elaine Ryder-Mills, Kara Sargus. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) and the National Cancer Research Network (NCRN). We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/ A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). We thank the SEARCH and EPIC teams, which were funded by a programme grant from Cancer Research UK (C490/A10124) and supported by the UK NIHR BRC at the University of Cambridge. We thank Breast Cancer Now and the Institute of Cancer Research (ICR) for support and funding of the UKBGS, and the study participants, study staff, and the doctors, nurses and other health-care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR BRC. UKGPCS would like to thank The Institute of Cancer Research and The Everyman Campaign for funding support. The UKGPCS acknowledges The Prostate Cancer Research Foundation, Prostate Action, The Orchid Cancer Appeal, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI), the NIHR funding to the NIHR Biomedical Research data managers and consultants for their work in the UKGPCS study and urologists and other persons involved in the planning, and data collection of the CAPS study. Genotyping of the OncoArray was funded by the US National Institutes of Health (NIH) (U19 CA 148537 for ELucidating Loci Involved in Prostate cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I). Additional analytic support was provided by NIH NCI U01 CA188392 (PI: Schumacher). The PRACTICAL consortium was supported by Cancer Research UK Grants C5047/ A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, European Commission's Seventh Framework Programme grant agreement no. 223175 (HEALTH-F2-2009-223175), and The National Institute of Health (NIH) Cancer PostCancer GWAS initiative grant: No. 1 U19 CA 148537-01 (the GAME-ON initiative). We would also like to thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. The APBC BioResource, which form part of the PRACTICAL consortium, consists of the following members: Wayne Tilley, Gail Risbridger, Renea Taylor, Judith A Clements, Lisa Horvath, Vanessa Hayes, Lisa Butler, Trina Yeadon, Allison Eckert, Pamela Saunders, Anne-Maree Haynes, Melissa Papargiris. At the MRC University of Glasgow Centre for Virus Research, funding was provided by Leukaemia Lymphoma Research (12022). The Scotland and Newcastle Epidemiological Study of Hodgkin Disease (SNEHD) was funded by the Kay Kendall Leukaemia Fund and the Young Adult Hodgkin Case–Control Study (YHCCS) and the Epidemiology and Cancer Statistics Group Lymphoma Case–Control Study (ELCCS) were funded by Bloodwise. German funding was provided by the German Cancer Aid, the Harald Huppert Foundations, The German Federal Ministry of Education and Research (eMed, Cliommics 01ZX1309B), the Multiple Myeloma Research Foundation, the Heinz Nixdorf Foundation (Germany), the Ministerium für Innovation, Wissenschaft und Forschung des Landes NordrheinWestfalen and the Faculty of Medicine University Duisburg–Essen. For their help with UK sample collection we thank Hayley Evans, James Griffin, Joanne Micic, Susan Blackmore, Beverley Smith, Deborah Hogben, Alison Butlin, Jill Wood, Margot Pelerin, Alison Hart, Katarzyna Tomczyk and Sarah Chilcott-Burns