Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study
Identifieur interne : 001E87 ( Pmc/Corpus ); précédent : 001E86; suivant : 001E88Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study
Auteurs : John C. Chambers ; Marie Loh ; Benjamin Lehne ; Alexander Drong ; Jennifer Kriebel ; Valeria Motta ; Simone Wahl ; Hannah R. Elliott ; Federica Rota ; William R. Scott ; Weihua Zhang ; Sian-Tsung Tan ; Gianluca Campanella ; Marc Chadeau-Hyam ; Loic Yengo ; Rebecca C. Richmond ; Martyna Adamowicz-Brice ; Uzma Afzal ; Kiymet Bozaoglu ; Zuan Yu Mok ; Hong Kiat Ng ; François Pattou ; Holger Prokisch ; Michelle Ann Rozario ; Letizia Tarantini ; James Abbott ; Mika Ala-Korpela ; Benedetta Albetti ; Ole Ammerpohl ; Pier Alberto Bertazzi ; Christine Blancher ; Robert Caiazzo ; John Danesh ; Tom R. Gaunt ; Simon De Lusignan ; Christian Gieger ; Thomas Illig ; Sujeet Jha ; Simon Jones ; Jeremy Jowett ; Antti J. Kangas ; Anuradhani Kasturiratne ; Norihiro Kato ; Navaratnam Kotea ; Sudhir Kowlessur ; Janne Pitk Niemi ; Prakash Punjabi ; Danish Saleheen ; Clemens Schafmayer ; Pasi Soininen ; E-Shyong Tai ; Barbara Thorand ; Jaakko Tuomilehto ; Ananda Rajitha Wickremasinghe ; Soterios A. Kyrtopoulos ; Timothy J. Aitman ; Christian Herder ; Jochen Hampe ; Stéphane Cauchi ; Caroline L. Relton ; Philippe Froguel ; Richie Soong ; Paolo Vineis ; Marjo-Riitta Jarvelin ; James Scott ; Harald Grallert ; Valentina Bollati ; Paul Elliott ; Mark I. Mccarthy ; Jaspal S. KoonerSource :
- The lancet. Diabetes & endocrinology [ 2213-8587 ] ; 2015.
Abstract
Indian Asians, who make up a quarter of the world’s population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes.
We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10−7. We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians.
1608 (11·9%) of 13 535 Indian Asians and 306 (4·3%) of 7066 Europeans developed type 2 diabetes over a mean of 8·5 years (SD 1·8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3·1 times (95% CI 2·8–3·6; p<0·0001) higher among Indian Asians than among Europeans, and remained 2·5 times (2·1–2·9; p<0·0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baseline glycaemic measures. The mean absolute difference in methylation level between type 2 diabetes cases and controls ranged from 0·5% (SD 0·1) to 1·1% (0·2). Methylation markers at five loci were associated with future type 2 diabetes incidence; the relative risk per 1% increase in methylation was 1·09 (95% CI 1·07–1·11; p=1·3 × 10−17) for
DNA methylation might provide new insights into the pathways underlying type 2 diabetes and offer new opportunities for risk stratification and prevention of type 2 diabetes among Indian Asians.
The European Union, the UK National Institute for Health Research, the Wellcome Trust, the UK Medical Research Council, Action on Hearing Loss, the UK Biotechnology and Biological Sciences Research Council, the Oak Foundation, the Economic and Social Research Council, Helmholtz Zentrum Munchen, the German Research Center for Environmental Health, the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the Munich Center for Health Sciences, the Ministry of Science and Research of the State of North Rhine-Westphalia, and the German Federal Ministry of Health.
Url:
DOI: 10.1016/S2213-8587(15)00127-8
PubMed: 26095709
PubMed Central: 4724884
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PMC:4724884Le document en format XML
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Mccarthy</name></author><author><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S" last="Kooner">Jaspal S. Kooner</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26095709</idno><idno type="pmc">4724884</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724884</idno><idno type="RBID">PMC:4724884</idno><idno type="doi">10.1016/S2213-8587(15)00127-8</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">001E87</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E87</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study</title><author><name sortKey="Chambers, John C" sort="Chambers, John C" uniqKey="Chambers J" first="John C" last="Chambers">John C. Chambers</name></author><author><name sortKey="Loh, Marie" sort="Loh, Marie" uniqKey="Loh M" first="Marie" last="Loh">Marie Loh</name></author><author><name sortKey="Lehne, Benjamin" sort="Lehne, Benjamin" uniqKey="Lehne B" first="Benjamin" last="Lehne">Benjamin Lehne</name></author><author><name sortKey="Drong, Alexander" sort="Drong, Alexander" uniqKey="Drong A" first="Alexander" last="Drong">Alexander Drong</name></author><author><name sortKey="Kriebel, Jennifer" sort="Kriebel, Jennifer" uniqKey="Kriebel J" first="Jennifer" last="Kriebel">Jennifer Kriebel</name></author><author><name sortKey="Motta, Valeria" sort="Motta, Valeria" uniqKey="Motta V" first="Valeria" last="Motta">Valeria Motta</name></author><author><name sortKey="Wahl, Simone" sort="Wahl, Simone" uniqKey="Wahl S" first="Simone" last="Wahl">Simone Wahl</name></author><author><name sortKey="Elliott, Hannah R" sort="Elliott, Hannah R" uniqKey="Elliott H" first="Hannah R" last="Elliott">Hannah R. Elliott</name></author><author><name sortKey="Rota, Federica" sort="Rota, Federica" uniqKey="Rota F" first="Federica" last="Rota">Federica Rota</name></author><author><name sortKey="Scott, William R" sort="Scott, William R" uniqKey="Scott W" first="William R" last="Scott">William R. Scott</name></author><author><name sortKey="Zhang, Weihua" sort="Zhang, Weihua" uniqKey="Zhang W" first="Weihua" last="Zhang">Weihua Zhang</name></author><author><name sortKey="Tan, Sian Tsung" sort="Tan, Sian Tsung" uniqKey="Tan S" first="Sian-Tsung" last="Tan">Sian-Tsung Tan</name></author><author><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name></author><author><name sortKey="Chadeau Hyam, Marc" sort="Chadeau Hyam, Marc" uniqKey="Chadeau Hyam M" first="Marc" last="Chadeau-Hyam">Marc Chadeau-Hyam</name></author><author><name sortKey="Yengo, Loic" sort="Yengo, Loic" uniqKey="Yengo L" first="Loic" last="Yengo">Loic Yengo</name></author><author><name sortKey="Richmond, Rebecca C" sort="Richmond, Rebecca C" uniqKey="Richmond R" first="Rebecca C" last="Richmond">Rebecca C. Richmond</name></author><author><name sortKey="Adamowicz Brice, Martyna" sort="Adamowicz Brice, Martyna" uniqKey="Adamowicz Brice M" first="Martyna" last="Adamowicz-Brice">Martyna Adamowicz-Brice</name></author><author><name sortKey="Afzal, Uzma" sort="Afzal, Uzma" uniqKey="Afzal U" first="Uzma" last="Afzal">Uzma Afzal</name></author><author><name sortKey="Bozaoglu, Kiymet" sort="Bozaoglu, Kiymet" uniqKey="Bozaoglu K" first="Kiymet" last="Bozaoglu">Kiymet Bozaoglu</name></author><author><name sortKey="Mok, Zuan Yu" sort="Mok, Zuan Yu" uniqKey="Mok Z" first="Zuan Yu" last="Mok">Zuan Yu Mok</name></author><author><name sortKey="Ng, Hong Kiat" sort="Ng, Hong Kiat" uniqKey="Ng H" first="Hong Kiat" last="Ng">Hong Kiat Ng</name></author><author><name sortKey="Pattou, Francois" sort="Pattou, Francois" uniqKey="Pattou F" first="François" last="Pattou">François Pattou</name></author><author><name sortKey="Prokisch, Holger" sort="Prokisch, Holger" uniqKey="Prokisch H" first="Holger" last="Prokisch">Holger Prokisch</name></author><author><name sortKey="Rozario, Michelle Ann" sort="Rozario, Michelle Ann" uniqKey="Rozario M" first="Michelle Ann" last="Rozario">Michelle Ann Rozario</name></author><author><name sortKey="Tarantini, Letizia" sort="Tarantini, Letizia" uniqKey="Tarantini L" first="Letizia" last="Tarantini">Letizia Tarantini</name></author><author><name sortKey="Abbott, James" sort="Abbott, James" uniqKey="Abbott J" first="James" last="Abbott">James Abbott</name></author><author><name sortKey="Ala Korpela, Mika" sort="Ala Korpela, Mika" uniqKey="Ala Korpela M" first="Mika" last="Ala-Korpela">Mika Ala-Korpela</name></author><author><name sortKey="Albetti, Benedetta" sort="Albetti, Benedetta" uniqKey="Albetti B" first="Benedetta" last="Albetti">Benedetta Albetti</name></author><author><name sortKey="Ammerpohl, Ole" sort="Ammerpohl, Ole" uniqKey="Ammerpohl O" first="Ole" last="Ammerpohl">Ole Ammerpohl</name></author><author><name sortKey="Bertazzi, Pier Alberto" sort="Bertazzi, Pier Alberto" uniqKey="Bertazzi P" first="Pier Alberto" last="Bertazzi">Pier Alberto Bertazzi</name></author><author><name sortKey="Blancher, Christine" sort="Blancher, Christine" uniqKey="Blancher C" first="Christine" last="Blancher">Christine Blancher</name></author><author><name sortKey="Caiazzo, Robert" sort="Caiazzo, Robert" uniqKey="Caiazzo R" first="Robert" last="Caiazzo">Robert Caiazzo</name></author><author><name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name></author><author><name sortKey="Gaunt, Tom R" sort="Gaunt, Tom R" uniqKey="Gaunt T" first="Tom R" last="Gaunt">Tom R. Gaunt</name></author><author><name sortKey="De Lusignan, Simon" sort="De Lusignan, Simon" uniqKey="De Lusignan S" first="Simon" last="De Lusignan">Simon De Lusignan</name></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name></author><author><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name></author><author><name sortKey="Jha, Sujeet" sort="Jha, Sujeet" uniqKey="Jha S" first="Sujeet" last="Jha">Sujeet Jha</name></author><author><name sortKey="Jones, Simon" sort="Jones, Simon" uniqKey="Jones S" first="Simon" last="Jones">Simon Jones</name></author><author><name sortKey="Jowett, Jeremy" sort="Jowett, Jeremy" uniqKey="Jowett J" first="Jeremy" last="Jowett">Jeremy Jowett</name></author><author><name sortKey="Kangas, Antti J" sort="Kangas, Antti J" uniqKey="Kangas A" first="Antti J" last="Kangas">Antti J. Kangas</name></author><author><name sortKey="Kasturiratne, Anuradhani" sort="Kasturiratne, Anuradhani" uniqKey="Kasturiratne A" first="Anuradhani" last="Kasturiratne">Anuradhani Kasturiratne</name></author><author><name sortKey="Kato, Norihiro" sort="Kato, Norihiro" uniqKey="Kato N" first="Norihiro" last="Kato">Norihiro Kato</name></author><author><name sortKey="Kotea, Navaratnam" sort="Kotea, Navaratnam" uniqKey="Kotea N" first="Navaratnam" last="Kotea">Navaratnam Kotea</name></author><author><name sortKey="Kowlessur, Sudhir" sort="Kowlessur, Sudhir" uniqKey="Kowlessur S" first="Sudhir" last="Kowlessur">Sudhir Kowlessur</name></author><author><name sortKey="Pitk Niemi, Janne" sort="Pitk Niemi, Janne" uniqKey="Pitk Niemi J" first="Janne" last="Pitk Niemi">Janne Pitk Niemi</name></author><author><name sortKey="Punjabi, Prakash" sort="Punjabi, Prakash" uniqKey="Punjabi P" first="Prakash" last="Punjabi">Prakash Punjabi</name></author><author><name sortKey="Saleheen, Danish" sort="Saleheen, Danish" uniqKey="Saleheen D" first="Danish" last="Saleheen">Danish Saleheen</name></author><author><name sortKey="Schafmayer, Clemens" sort="Schafmayer, Clemens" uniqKey="Schafmayer C" first="Clemens" last="Schafmayer">Clemens Schafmayer</name></author><author><name sortKey="Soininen, Pasi" sort="Soininen, Pasi" uniqKey="Soininen P" first="Pasi" last="Soininen">Pasi Soininen</name></author><author><name sortKey="Tai, E Shyong" sort="Tai, E Shyong" uniqKey="Tai E" first="E-Shyong" last="Tai">E-Shyong Tai</name></author><author><name sortKey="Thorand, Barbara" sort="Thorand, Barbara" uniqKey="Thorand B" first="Barbara" last="Thorand">Barbara Thorand</name></author><author><name sortKey="Tuomilehto, Jaakko" sort="Tuomilehto, Jaakko" uniqKey="Tuomilehto J" first="Jaakko" last="Tuomilehto">Jaakko Tuomilehto</name></author><author><name sortKey="Wickremasinghe, Ananda Rajitha" sort="Wickremasinghe, Ananda Rajitha" uniqKey="Wickremasinghe A" first="Ananda Rajitha" last="Wickremasinghe">Ananda Rajitha Wickremasinghe</name></author><author><name sortKey="Kyrtopoulos, Soterios A" sort="Kyrtopoulos, Soterios A" uniqKey="Kyrtopoulos S" first="Soterios A" last="Kyrtopoulos">Soterios A. Kyrtopoulos</name></author><author><name sortKey="Aitman, Timothy J" sort="Aitman, Timothy J" uniqKey="Aitman T" first="Timothy J" last="Aitman">Timothy J. Aitman</name></author><author><name sortKey="Herder, Christian" sort="Herder, Christian" uniqKey="Herder C" first="Christian" last="Herder">Christian Herder</name></author><author><name sortKey="Hampe, Jochen" sort="Hampe, Jochen" uniqKey="Hampe J" first="Jochen" last="Hampe">Jochen Hampe</name></author><author><name sortKey="Cauchi, Stephane" sort="Cauchi, Stephane" uniqKey="Cauchi S" first="Stéphane" last="Cauchi">Stéphane Cauchi</name></author><author><name sortKey="Relton, Caroline L" sort="Relton, Caroline L" uniqKey="Relton C" first="Caroline L" last="Relton">Caroline L. Relton</name></author><author><name sortKey="Froguel, Philippe" sort="Froguel, Philippe" uniqKey="Froguel P" first="Philippe" last="Froguel">Philippe Froguel</name></author><author><name sortKey="Soong, Richie" sort="Soong, Richie" uniqKey="Soong R" first="Richie" last="Soong">Richie Soong</name></author><author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name></author><author><name sortKey="Jarvelin, Marjo Riitta" sort="Jarvelin, Marjo Riitta" uniqKey="Jarvelin M" first="Marjo-Riitta" last="Jarvelin">Marjo-Riitta Jarvelin</name></author><author><name sortKey="Scott, James" sort="Scott, James" uniqKey="Scott J" first="James" last="Scott">James Scott</name></author><author><name sortKey="Grallert, Harald" sort="Grallert, Harald" uniqKey="Grallert H" first="Harald" last="Grallert">Harald Grallert</name></author><author><name sortKey="Bollati, Valentina" sort="Bollati, Valentina" uniqKey="Bollati V" first="Valentina" last="Bollati">Valentina Bollati</name></author><author><name sortKey="Elliott, Paul" sort="Elliott, Paul" uniqKey="Elliott P" first="Paul" last="Elliott">Paul Elliott</name></author><author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name></author><author><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S" last="Kooner">Jaspal S. Kooner</name></author></analytic><series><title level="j">The lancet. Diabetes & endocrinology</title><idno type="ISSN">2213-8587</idno><idno type="eISSN">2213-8595</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><sec id="S1"><title>Background</title><p id="P3">Indian Asians, who make up a quarter of the world’s population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes.</p></sec><sec id="S2"><title>Methods</title><p id="P4">We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10<sup>−7</sup>. We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians.</p></sec><sec id="S3"><title>Findings</title><p id="P5">1608 (11·9%) of 13 535 Indian Asians and 306 (4·3%) of 7066 Europeans developed type 2 diabetes over a mean of 8·5 years (SD 1·8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3·1 times (95% CI 2·8–3·6; p<0·0001) higher among Indian Asians than among Europeans, and remained 2·5 times (2·1–2·9; p<0·0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baseline glycaemic measures. The mean absolute difference in methylation level between type 2 diabetes cases and controls ranged from 0·5% (SD 0·1) to 1·1% (0·2). Methylation markers at five loci were associated with future type 2 diabetes incidence; the relative risk per 1% increase in methylation was 1·09 (95% CI 1·07–1·11; p=1·3 × 10<sup>−17</sup>) for <italic>ABCG1</italic>, 0·94 (0·92–0·95; p=4·2 × 10<sup>−11</sup>) for <italic>PHOSPHO1</italic>, 0·94 (0·92–0·96; p=1·4 × 10<sup>−9</sup>) for <italic>SOCS3</italic>, 1·07 (1·04–1·09; p=2·1 × 10<sup>−10</sup>) for <italic>SREBF1</italic>, and 0·92 (0·90–0·94; p=1·2 × 10<sup>−17</sup>) for <italic>TXNIP</italic>. A methylation score combining results for the five loci was associated with future type 2 diabetes incidence (relative risk quartile 4 <italic>vs</italic> quartile 1 3·51, 95% CI 2·79–4·42; p=1·3 × 10<sup>−26</sup>), and was independent of established risk factors. Methylation score was higher among Indian Asians than Europeans (p=1 × 10<sup>−34</sup>).</p></sec><sec id="S4"><title>Interpretation</title><p id="P6">DNA methylation might provide new insights into the pathways underlying type 2 diabetes and offer new opportunities for risk stratification and prevention of type 2 diabetes among Indian Asians.</p></sec><sec id="S5"><title>Funding</title><p id="P7">The European Union, the UK National Institute for Health Research, the Wellcome Trust, the UK Medical Research Council, Action on Hearing Loss, the UK Biotechnology and Biological Sciences Research Council, the Oak Foundation, the Economic and Social Research Council, Helmholtz Zentrum Munchen, the German Research Center for Environmental Health, the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the Munich Center for Health Sciences, the Ministry of Science and Research of the State of North Rhine-Westphalia, and the German Federal Ministry of Health.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101618821</journal-id><journal-id journal-id-type="pubmed-jr-id">41837</journal-id><journal-id journal-id-type="nlm-ta">Lancet Diabetes Endocrinol</journal-id><journal-id journal-id-type="iso-abbrev">Lancet Diabetes Endocrinol</journal-id><journal-title-group><journal-title>The lancet. Diabetes & endocrinology</journal-title></journal-title-group><issn pub-type="ppub">2213-8587</issn><issn pub-type="epub">2213-8595</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26095709</article-id><article-id pub-id-type="pmc">4724884</article-id><article-id pub-id-type="doi">10.1016/S2213-8587(15)00127-8</article-id><article-id pub-id-type="manuscript">EMS66669</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Chambers</surname><given-names>John C</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Loh</surname><given-names>Marie</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Lehne</surname><given-names>Benjamin</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Drong</surname><given-names>Alexander</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Kriebel</surname><given-names>Jennifer</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Motta</surname><given-names>Valeria</given-names></name></contrib><contrib contrib-type="author"><name><surname>Wahl</surname><given-names>Simone</given-names></name></contrib><contrib contrib-type="author"><name><surname>Elliott</surname><given-names>Hannah R</given-names></name></contrib><contrib contrib-type="author"><name><surname>Rota</surname><given-names>Federica</given-names></name></contrib><contrib contrib-type="author"><name><surname>Scott</surname><given-names>William R</given-names></name></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Weihua</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tan</surname><given-names>Sian-Tsung</given-names></name></contrib><contrib contrib-type="author"><name><surname>Campanella</surname><given-names>Gianluca</given-names></name></contrib><contrib contrib-type="author"><name><surname>Chadeau-Hyam</surname><given-names>Marc</given-names></name></contrib><contrib contrib-type="author"><name><surname>Yengo</surname><given-names>Loic</given-names></name></contrib><contrib contrib-type="author"><name><surname>Richmond</surname><given-names>Rebecca C</given-names></name></contrib><contrib contrib-type="author"><name><surname>Adamowicz-Brice</surname><given-names>Martyna</given-names></name></contrib><contrib contrib-type="author"><name><surname>Afzal</surname><given-names>Uzma</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bozaoglu</surname><given-names>Kiymet</given-names></name></contrib><contrib contrib-type="author"><name><surname>Mok</surname><given-names>Zuan Yu</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ng</surname><given-names>Hong Kiat</given-names></name></contrib><contrib contrib-type="author"><name><surname>Pattou</surname><given-names>François</given-names></name></contrib><contrib contrib-type="author"><name><surname>Prokisch</surname><given-names>Holger</given-names></name></contrib><contrib contrib-type="author"><name><surname>Rozario</surname><given-names>Michelle Ann</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tarantini</surname><given-names>Letizia</given-names></name></contrib><contrib contrib-type="author"><name><surname>Abbott</surname><given-names>James</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ala-Korpela</surname><given-names>Mika</given-names></name></contrib><contrib contrib-type="author"><name><surname>Albetti</surname><given-names>Benedetta</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ammerpohl</surname><given-names>Ole</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bertazzi</surname><given-names>Pier Alberto</given-names></name></contrib><contrib contrib-type="author"><name><surname>Blancher</surname><given-names>Christine</given-names></name></contrib><contrib contrib-type="author"><name><surname>Caiazzo</surname><given-names>Robert</given-names></name></contrib><contrib contrib-type="author"><name><surname>Danesh</surname><given-names>John</given-names></name></contrib><contrib contrib-type="author"><name><surname>Gaunt</surname><given-names>Tom R</given-names></name></contrib><contrib contrib-type="author"><name><surname>de Lusignan</surname><given-names>Simon</given-names></name></contrib><contrib contrib-type="author"><name><surname>Gieger</surname><given-names>Christian</given-names></name></contrib><contrib contrib-type="author"><name><surname>Illig</surname><given-names>Thomas</given-names></name></contrib><contrib contrib-type="author"><name><surname>Jha</surname><given-names>Sujeet</given-names></name></contrib><contrib contrib-type="author"><name><surname>Jones</surname><given-names>Simon</given-names></name></contrib><contrib contrib-type="author"><name><surname>Jowett</surname><given-names>Jeremy</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kangas</surname><given-names>Antti J</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kasturiratne</surname><given-names>Anuradhani</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kato</surname><given-names>Norihiro</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kotea</surname><given-names>Navaratnam</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kowlessur</surname><given-names>Sudhir</given-names></name></contrib><contrib contrib-type="author"><name><surname>Pitkäniemi</surname><given-names>Janne</given-names></name></contrib><contrib contrib-type="author"><name><surname>Punjabi</surname><given-names>Prakash</given-names></name></contrib><contrib contrib-type="author"><name><surname>Saleheen</surname><given-names>Danish</given-names></name></contrib><contrib contrib-type="author"><name><surname>Schafmayer</surname><given-names>Clemens</given-names></name></contrib><contrib contrib-type="author"><name><surname>Soininen</surname><given-names>Pasi</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tai</surname><given-names>E-Shyong</given-names></name></contrib><contrib contrib-type="author"><name><surname>Thorand</surname><given-names>Barbara</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tuomilehto</surname><given-names>Jaakko</given-names></name></contrib><contrib contrib-type="author"><name><surname>Wickremasinghe</surname><given-names>Ananda Rajitha</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kyrtopoulos</surname><given-names>Soterios A</given-names></name></contrib><contrib contrib-type="author"><name><surname>Aitman</surname><given-names>Timothy J</given-names></name></contrib><contrib contrib-type="author"><name><surname>Herder</surname><given-names>Christian</given-names></name></contrib><contrib contrib-type="author"><name><surname>Hampe</surname><given-names>Jochen</given-names></name></contrib><contrib contrib-type="author"><name><surname>Cauchi</surname><given-names>Stéphane</given-names></name></contrib><contrib contrib-type="author"><name><surname>Relton</surname><given-names>Caroline L</given-names></name></contrib><contrib contrib-type="author"><name><surname>Froguel</surname><given-names>Philippe</given-names></name></contrib><contrib contrib-type="author"><name><surname>Soong</surname><given-names>Richie</given-names></name></contrib><contrib contrib-type="author"><name><surname>Vineis</surname><given-names>Paolo</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Jarvelin</surname><given-names>Marjo-Riitta</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Scott</surname><given-names>James</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Grallert</surname><given-names>Harald</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Bollati</surname><given-names>Valentina</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Elliott</surname><given-names>Paul</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>McCarthy</surname><given-names>Mark I</given-names></name></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Kooner</surname><given-names>Jaspal S</given-names></name></contrib></contrib-group><aff id="A1"><bold>Department of Epidemiology and Biostatistics</bold> (J C Chambers PhD, M Loh PhD, B Lehne PhD, W R Scott MRCP, W Zhang PhD, G Campanella MSc, M Chadeau-Hyam PhD, U Afzal MRCP, Prof P Froguel PhD, Prof P Vineis MD, Prof M-R Jarvelin PhD, Prof P Elliott PhD)<bold>, MRC-PHE Centre for Environment and Health</bold> (J C Chambers, Prof M-R Jarvelin, Prof P Elliott, Prof J S Kooner FRCP)<bold>, National Heart and Lung Institute</bold> (W R Scott, S-T Tan MRCP, Prof J Scott PhD, Prof J S Kooner)<bold>, and Bioinformatics Support Service</bold> (J Abbott PhD)<bold>, Imperial College London, London, UK; Ealing Hospital NHS Trust, Middlesex, UK</bold> (J C Chambers, W Zhang, S-T Tan, U Afzal, Prof J S Kooner)<bold>; Imperial College Healthcare NHS Trust, London, UK</bold> (J C Chambers, P Punjabi FRCS, Prof J S Kooner)<bold>; Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore</bold> (M Loh)<bold>; High Throughput Genomics, Oxford Genomic Centre</bold> (C Blancher PhD)<bold>, Wellcome Trust Centre for Human Genetics</bold> (A Drong PhD, Prof M I McCarthy MD)<bold>, and Oxford Centre for Diabetes, Endocrinology and Metabolism</bold> (Prof M I McCarthy)<bold>, University of Oxford, Oxford, UK; Research Unit of Molecular Epidemiology</bold> (J Kriebel PhD, S Wahl MSc, C Gieger PhD, H Grallert PhD)<bold>, Institute of Genetic Epidemiology</bold> (C Gieger)<bold>, Institute of Epidemiology II</bold> (J Kriebel, S Wahl, C Gieger, B Thorand PhD, H Grallert)<bold>, and Institute of Human Genetics</bold> (H Prokisch PhD)<bold>, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research, Munich, Germany</bold> (J Kriebel, S Wahl, B Thorand, H Grallert)<bold>; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy</bold> (V Motta PhD, F Rota PhD, L Tarantini PhD, B Albetti PhD, Prof P A Bertazzi MD, V Bollati PhD)<bold>; Computational Medicine</bold> (Prof M Ala-Korpela PhD)<bold>, MRC Integrative Epidemiology Unit, School of Social and Community Medicine</bold> (H R Elliott Dip Biol, R C Richmond BA, R Caiazzo PhD, T R Gaunt FRCP, Prof C L Relton PhD)<bold>, University of Bristol, Bristol, UK; European Genomic Institute for Diabetes, Lille, France</bold> (L Yengo PhD, Prof F Pattou PhD, R Caiazzo, S Cauchi PhD, Prof P Froguel)<bold>; CNRS UMR8199, Pasteur Institute of Lille, Lille, France</bold> (L Yengo, S Cauchi, Prof P Froguel)<bold>; Lille 2 University, Lille, France</bold> (L Yengo, Prof F Pattou, S Cauchi, Prof P Froguel)<bold>; Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London, UK</bold> (M Adamowicz-Brice PhD, Prof T J Aitman PhD)<bold>; Genomics and Systems Biology, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia</bold> (K Bozaoglu PhD, R Caiazzo, J Jowett PhD)<bold>; Cancer Science Institute of Singapore</bold> (Z Y Mok BSc, H K Ng BSc, M A Rozario BSc, R Soong PhD)<bold>, Department of Medicine, Yong Loo Lin School of Medicine</bold> (E-S Tai PhD)<bold>, and Saw Swee Hock School of Public Health</bold> (E-S Tai)<bold>, National University of Singapore, Singapore; Inserm UMR859, Claude-Huriez Hospital, Lille, France</bold> (Prof F Pattou)<bold>; Institute of Human Genetics, Technical University Munich, München, Germany</bold> (H Prokisch)<bold>; Computational Medicine</bold> (Prof M Ala-Korpela, A J Kangas MSc, P Soininen PhD)<bold>, Institute of Health Sciences</bold> (M Loh, Prof M-R Jarvelin)<bold>and Biocenter Oulu</bold> (Prof M-R Jarvelin)<bold>, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland</bold> (Prof M Ala-Korpela, P Soininen)<bold>; Unit of Primary Care</bold> (Prof M-R Jarvelin)<bold>, Oulu University Hospital</bold> (Prof M Ala-Korpela)<bold>, Oulu, Finland; Institute of Human Genetics</bold> (Prof O Ammerpohl PhD)<bold>and Department of Visceral and Thoracic Surgery</bold> (Prof C Schafmayer MD)<bold>, University Hospital Schleswig-Holstein, Kiel Campus, Kiel, Germany; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</bold> (Prof J Danesh FRCP)<bold>; University of Surrey, Guildford, UK</bold> (Prof S de Lusignan PhD, Prof S Jones PhD)<bold>; Hannover Medical School, Hannover Unified Biobank, Hannover, Germany</bold> (Prof T Illig PhD)<bold>; Department of Endocrinology, Diabetes and Obesity, Max Healthcare, New Delhi, India</bold> (S Jha MRCP)<bold>; Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka</bold> (A Kasturiratne MD, Prof A R Wickremasinghe PhD)<bold>; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</bold> (N Kato PhD)<bold>; Department of Health Sciences, University of Mauritius, Reduit, Mauritius</bold> (N Kotea PhD)<bold>; Ministry of Health and Quality of Life, Port louis, Mauritius</bold> (S Kowlessur Dip Pub Health Admin)<bold>; Hjelt Institute, School of Medicine</bold> (J Pitkäniemi PhD)<bold>and Department of Public Health</bold> (Prof J Tuomilehto PhD)<bold>, University of Helsinki, Finland; Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland</bold> (J Pitkäniemi)<bold>; Center for Non-Communicable Diseases, Karachi, Pakistan</bold> (D Saleheen PhD)<bold>; Department of Public Health and Primary Care, University of Cambridge Strangeways Research Laboratory, Cambridge, UK</bold> (D Saleheen)<bold>; Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA</bold> (D Saleheen)<bold>; Duke National University of Singapore Graduate Medical School, Singapore, Singapore</bold> (E-S Tai)<bold>; National Hellenic Research Foundation, Institute of Biology, Pharmaceutical Chemistry and Biotechnology, Athens, Greece</bold> (Prof S A Kyrtopoulos PhD)<bold>; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany</bold> (C Herder PhD)<bold>; German Center for Diabetes Research, Düsseldorf, Germany</bold> (C Herder)<bold>; Medical Department 1, University Hospital of the Technical University Dresden, Dresden, Germany</bold> (Prof J Hampe MD)<bold>; Department of Pathology, National University Hospital, Singapore, Singapore</bold> (R Soong)<bold>; HuGeF Foundation, Torino, Italy</bold> (Prof P Vineis)<bold>; and Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK</bold> (Prof M I McCarthy)</aff><author-notes><corresp id="CR1">Correspondence to: Dr John C Chambers, Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK, <email>john.chambers@ic.ac.uk</email> or Prof Jaspal S Kooner, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK, <email>j.kooner@ic.ac.uk</email></corresp><fn id="FN2"><p id="P1"><bold>Contributors</bold></p><p id="P2">JCC, PAB, JD, SJh, JJ, NKa, JP, DS, E-ST, JT, ARW, M-RJ, JS, VB, PE, MIM, and JSK conceived and designed the study. JCC, JK, HRE, WRS, S-TT, RCR, UA, KB, RC, JD, TRG, SdL, CG, TI, SJh, SJo, AK, NKo, SK, PP, BT, ARW, CH, SC, CLR, PF, PV, JS, HG, PE, and JSK were involved in participant recruitment and characterisation. JCC, ML, AD, VM, SW, HRE, FR, WRS, WZ, S-TT, GC, MC-H, LY, RCR, MA-B, ZYM, HKN, FP, HP, MAR, LT, JA, MA-K, BA, OA, PAB, CB, TRG, CG, TI, JJ, AJK, NKo, SK, CS, PS, BT, SAK, TJA, CH, JH, SC, CLR, PF, RS, PV, M-RJ, JS, HG, VB, and JSK generated molecular phenotype data. JCC, ML, BL, AD, JK, SW, HRE, WZ, GC, LY, RCR, JP, CLR, M-RJ, PE, MIM, and JSK were involved in statistical analyses. JCC, ML, BL, AD, CG, SJh, NKa, E-ST, ARW, RS, PV, M-RJ, JS, HG, VB, PE, MIM, and JSK wrote the manuscript draft. All authors contributed to, read, and approved the final version of the manuscript.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>19</day><month>1</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>18</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>7</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>25</day><month>1</month><year>2016</year></pub-date><volume>3</volume><issue>7</issue><fpage>526</fpage><lpage>534</lpage><pmc-comment>elocation-id from pubmed: 10.1016/S2213-8587(15)00127-8</pmc-comment>
<abstract><title>Summary</title><sec id="S1"><title>Background</title><p id="P3">Indian Asians, who make up a quarter of the world’s population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes.</p></sec><sec id="S2"><title>Methods</title><p id="P4">We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10<sup>−7</sup>. We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians.</p></sec><sec id="S3"><title>Findings</title><p id="P5">1608 (11·9%) of 13 535 Indian Asians and 306 (4·3%) of 7066 Europeans developed type 2 diabetes over a mean of 8·5 years (SD 1·8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3·1 times (95% CI 2·8–3·6; p<0·0001) higher among Indian Asians than among Europeans, and remained 2·5 times (2·1–2·9; p<0·0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baseline glycaemic measures. The mean absolute difference in methylation level between type 2 diabetes cases and controls ranged from 0·5% (SD 0·1) to 1·1% (0·2). Methylation markers at five loci were associated with future type 2 diabetes incidence; the relative risk per 1% increase in methylation was 1·09 (95% CI 1·07–1·11; p=1·3 × 10<sup>−17</sup>) for <italic>ABCG1</italic>, 0·94 (0·92–0·95; p=4·2 × 10<sup>−11</sup>) for <italic>PHOSPHO1</italic>, 0·94 (0·92–0·96; p=1·4 × 10<sup>−9</sup>) for <italic>SOCS3</italic>, 1·07 (1·04–1·09; p=2·1 × 10<sup>−10</sup>) for <italic>SREBF1</italic>, and 0·92 (0·90–0·94; p=1·2 × 10<sup>−17</sup>) for <italic>TXNIP</italic>. A methylation score combining results for the five loci was associated with future type 2 diabetes incidence (relative risk quartile 4 <italic>vs</italic> quartile 1 3·51, 95% CI 2·79–4·42; p=1·3 × 10<sup>−26</sup>), and was independent of established risk factors. Methylation score was higher among Indian Asians than Europeans (p=1 × 10<sup>−34</sup>).</p></sec><sec id="S4"><title>Interpretation</title><p id="P6">DNA methylation might provide new insights into the pathways underlying type 2 diabetes and offer new opportunities for risk stratification and prevention of type 2 diabetes among Indian Asians.</p></sec><sec id="S5"><title>Funding</title><p id="P7">The European Union, the UK National Institute for Health Research, the Wellcome Trust, the UK Medical Research Council, Action on Hearing Loss, the UK Biotechnology and Biological Sciences Research Council, the Oak Foundation, the Economic and Social Research Council, Helmholtz Zentrum Munchen, the German Research Center for Environmental Health, the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the Munich Center for Health Sciences, the Ministry of Science and Research of the State of North Rhine-Westphalia, and the German Federal Ministry of Health.</p></sec></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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