9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci ( P < 5 × 10 −8). Several of these contain candidate genes ( TINF2, PARP1, TERF1, ATM and POT1) with potential roles in telomere biology and DNA repair mechanisms. Meta-analyses with additional 37,505 European individuals reveals six more genome-wide loci, including associations at MPHOSPH6, NKX2-3 and TYMS. We demonstrate that longer LTL associates with protection against respiratory disease mortality [HR = 0.854(0.804–0.906), P = 1.88 × 10 −7] in the Singaporean Chinese samples. We further show that the LTL reducing SNP rs7253490 associates with respiratory infections ( P = 7.44 × 10 −4) although this effect may not be strongly mediated through LTL. Our data expands on the genetic basis of LTL and may indicate on a potential role of LTL in immune competence.

          Abstract

          Shortening of leukocyte telomere length (LTL) is associated with age and increased risk for various chronic diseases. Here, the authors report genome-wide association studies for LTL in Singaporean Chinese populations and find that longer LTL associates with less severe outcomes of respiratory disease phenotypes.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

          While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (Database of Immune Cell Expression, Expression quantitative trait loci (eQTLs) and Epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis -eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis -association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis ( http://dice-database.org ). In Brief: Surveying gene expression and SNP genotypes across immune cell types from healthy humans reveals cis-eQTLs affecting over half of all expressed genes and demonstrates that variant effects often manifest in cell types other than those with highest gene expression.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Singapore Chinese Health Study: development, validation, and calibration of the quantitative food frequency questionnaire.

            This report describes the development and validation/calibration of a structured food frequency questionnaire for use in a large-scale cohort study of diet and health in Chinese men and women aged 45-74 years in Singapore, the development of a food composition database for analysis of the dietary data, and the results of the dietary validation/calibration study. The present calibration study comparing estimated intakes from 24-hour recalls with those from the food frequency questionnaires revealed correlations of 0.24-0.79 for energy and nutrients among the Singapore Chinese, which are comparable to the correlation coefficients reported in calibration studies of other populations. We also report on the nutritional profiles of Singapore Chinese on the basis of results of 1,880 24-hour dietary recalls conducted on 1,022 (425 men and 597 women) cohort subjects. Comparisons with age-adjusted corresponding values for US whites and blacks show distinct differences in dietary intakes between the Singapore and US populations. The Singapore cohort will be followed prospectively to identify dietary associations with cancer risk and other health outcomes.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR

              Telomere length/DNA content has been measured in epidemiological/clinical settings with the goal of testing a host of hypotheses related to the biology of human aging, but often the conclusions of these studies have been inconsistent. These inconsistencies may stem from various reasons, including the use of different telomere length measurement techniques. Here, we report the first impartial evaluation of measurements of leukocyte telomere length by Southern blot of the terminal restriction fragments and quantitative PCR (qPCR) of telomere DNA content, expressed as the ratio of telomeric product (T)/single copy gene (S) product. Blind measurements on the same samples from 50 donors were performed in two independent laboratories on two different occasions. Both the qPCR and Southern blots displayed highly reproducible results as shown by r values > 0.9 for the correlations between results obtained by either method on two occasions. The inter-assay CV measurement for the qPCR was 6.45%, while that of the Southern blots was 1.74%. The relation between the results generated by Southern blots versus those generated by qPCR deviated from linearity. We discuss the ramifications of these findings with regard to measurements of telomere length/DNA content in epidemiological/clinical circumstances.
                Bookmark

                Author and article information

                Contributors
                khorcc@gis.a-star.edu.sg
                paehck@nus.edu.sg
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                6 June 2019
                6 June 2019
                2019
                : 10
                : 2491
                Affiliations
                [1 ]ISNI 0000 0004 0637 0221, GRID grid.185448.4, Genome Institute of Singapore, , Agency for Science, Technology and Research, ; Singapore, 138672 Singapore
                [2 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, Department of Paediatrics, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, 119228 Singapore
                [3 ]ISNI 0000 0004 0451 6143, GRID grid.410759.e, Khoo Teck Puat – National University Children’s Medical Institute, , National University Health System, ; Singapore, 119074 Singapore
                [4 ]ISNI 0000 0004 0451 6370, GRID grid.415203.1, Clinical Research Unit, , Khoo Teck Puat Hospital, ; Singapore, 768828 Singapore
                [5 ]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, , University of Pittsburgh, ; Pittsburgh, PA 15232 USA
                [6 ]ISNI 0000000419368657, GRID grid.17635.36, University of Minnesota Genomics Center, , University of Minnesota, ; Minneapolis, MN 55455 USA
                [7 ]ISNI 0000 0004 0451 6370, GRID grid.415203.1, Diabetes Centre, , Khoo Teck Puat Hospital, ; Singapore, 768828 Singapore
                [8 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, Saw Swee Hock School of Public Health, , National University of Singapore, ; Singapore, 117549 Singapore
                [9 ]ISNI 0000 0004 1937 0538, GRID grid.9619.7, School of Public Health and Community Medicine, , Hebrew University of Jerusalem, ; Jerusalem, 12272 Israel
                [10 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, Department of Medicine, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, 117597 Singapore
                [11 ]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Department of Epidemiology, Graduate School of Public Health, , University of Pittsburgh, ; Pittsburgh, PA 15261 USA
                [12 ]ISNI 0000 0004 0385 0924, GRID grid.428397.3, Health Systems and Services Research, , Duke-NUS Medical School Singapore, ; Singapore, 169857 Singapore
                [13 ]ISNI 0000 0000 9960 1711, GRID grid.419272.b, Singapore Eye Research Institute, , Singapore National Eye Centre, ; Singapore, 169856 Singapore
                Author information
                http://orcid.org/0000-0001-6608-2051
                http://orcid.org/0000-0002-7060-2213
                http://orcid.org/0000-0001-8876-0706
                http://orcid.org/0000-0002-3822-7759
                http://orcid.org/0000-0002-3255-3019
                http://orcid.org/0000-0002-4620-3108
                http://orcid.org/0000-0002-1128-4729
                http://orcid.org/0000-0002-7309-9473
                Article
                10443
                10.1038/s41467-019-10443-2
                6554354
                31171785
                1e7885aa-2221-4d78-a35d-94c12baf127d
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 21 December 2018
                : 9 May 2019
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                genetics,genome-wide association studies,telomeres,genetics research
                Uncategorized
                genetics, genome-wide association studies, telomeres, genetics research

                Comments

                Comment on this article