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 : 002E45 ( Main/Exploration ); précédent : 002E44; suivant : 002E46Epigenome-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.
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DOI: 10.1016/S2213-8587(15)00127-8
PubMed: 26095709
PubMed Central: 4724884
Affiliations:
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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><affiliations><list></list><tree><noCountry><name sortKey="Abbott, James" sort="Abbott, James" uniqKey="Abbott J" first="James" last="Abbott">James Abbott</name><name sortKey="Adamowicz Brice, Martyna" sort="Adamowicz Brice, Martyna" uniqKey="Adamowicz Brice M" first="Martyna" last="Adamowicz-Brice">Martyna Adamowicz-Brice</name><name sortKey="Afzal, Uzma" sort="Afzal, Uzma" uniqKey="Afzal U" first="Uzma" last="Afzal">Uzma Afzal</name><name sortKey="Aitman, Timothy J" sort="Aitman, Timothy J" uniqKey="Aitman T" first="Timothy J" last="Aitman">Timothy J. Aitman</name><name sortKey="Ala Korpela, Mika" sort="Ala Korpela, Mika" uniqKey="Ala Korpela M" first="Mika" last="Ala-Korpela">Mika Ala-Korpela</name><name sortKey="Albetti, Benedetta" sort="Albetti, Benedetta" uniqKey="Albetti B" first="Benedetta" last="Albetti">Benedetta Albetti</name><name sortKey="Ammerpohl, Ole" sort="Ammerpohl, Ole" uniqKey="Ammerpohl O" first="Ole" last="Ammerpohl">Ole Ammerpohl</name><name sortKey="Bertazzi, Pier Alberto" sort="Bertazzi, Pier Alberto" uniqKey="Bertazzi P" first="Pier Alberto" last="Bertazzi">Pier Alberto Bertazzi</name><name sortKey="Blancher, Christine" sort="Blancher, Christine" uniqKey="Blancher C" first="Christine" last="Blancher">Christine Blancher</name><name sortKey="Bollati, Valentina" sort="Bollati, Valentina" uniqKey="Bollati V" first="Valentina" last="Bollati">Valentina Bollati</name><name sortKey="Bozaoglu, Kiymet" sort="Bozaoglu, Kiymet" uniqKey="Bozaoglu K" first="Kiymet" last="Bozaoglu">Kiymet Bozaoglu</name><name sortKey="Caiazzo, Robert" sort="Caiazzo, Robert" uniqKey="Caiazzo R" first="Robert" last="Caiazzo">Robert Caiazzo</name><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name><name sortKey="Cauchi, Stephane" sort="Cauchi, Stephane" uniqKey="Cauchi S" first="Stéphane" last="Cauchi">Stéphane Cauchi</name><name sortKey="Chadeau Hyam, Marc" sort="Chadeau Hyam, Marc" uniqKey="Chadeau Hyam M" first="Marc" last="Chadeau-Hyam">Marc Chadeau-Hyam</name><name sortKey="Chambers, John C" sort="Chambers, John C" uniqKey="Chambers J" first="John C" last="Chambers">John C. Chambers</name><name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name><name sortKey="De Lusignan, Simon" sort="De Lusignan, Simon" uniqKey="De Lusignan S" first="Simon" last="De Lusignan">Simon De Lusignan</name><name sortKey="Drong, Alexander" sort="Drong, Alexander" uniqKey="Drong A" first="Alexander" last="Drong">Alexander Drong</name><name sortKey="Elliott, Hannah R" sort="Elliott, Hannah R" uniqKey="Elliott H" first="Hannah R" last="Elliott">Hannah R. Elliott</name><name sortKey="Elliott, Paul" sort="Elliott, Paul" uniqKey="Elliott P" first="Paul" last="Elliott">Paul Elliott</name><name sortKey="Froguel, Philippe" sort="Froguel, Philippe" uniqKey="Froguel P" first="Philippe" last="Froguel">Philippe Froguel</name><name sortKey="Gaunt, Tom R" sort="Gaunt, Tom R" uniqKey="Gaunt T" first="Tom R" last="Gaunt">Tom R. Gaunt</name><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><name sortKey="Grallert, Harald" sort="Grallert, Harald" uniqKey="Grallert H" first="Harald" last="Grallert">Harald Grallert</name><name sortKey="Hampe, Jochen" sort="Hampe, Jochen" uniqKey="Hampe J" first="Jochen" last="Hampe">Jochen Hampe</name><name sortKey="Herder, Christian" sort="Herder, Christian" uniqKey="Herder C" first="Christian" last="Herder">Christian Herder</name><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><name sortKey="Jarvelin, Marjo Riitta" sort="Jarvelin, Marjo Riitta" uniqKey="Jarvelin M" first="Marjo-Riitta" last="Jarvelin">Marjo-Riitta Jarvelin</name><name sortKey="Jha, Sujeet" sort="Jha, Sujeet" uniqKey="Jha S" first="Sujeet" last="Jha">Sujeet Jha</name><name sortKey="Jones, Simon" sort="Jones, Simon" uniqKey="Jones S" first="Simon" last="Jones">Simon Jones</name><name sortKey="Jowett, Jeremy" sort="Jowett, Jeremy" uniqKey="Jowett J" first="Jeremy" last="Jowett">Jeremy Jowett</name><name sortKey="Kangas, Antti J" sort="Kangas, Antti J" uniqKey="Kangas A" first="Antti J" last="Kangas">Antti J. Kangas</name><name sortKey="Kasturiratne, Anuradhani" sort="Kasturiratne, Anuradhani" uniqKey="Kasturiratne A" first="Anuradhani" last="Kasturiratne">Anuradhani Kasturiratne</name><name sortKey="Kato, Norihiro" sort="Kato, Norihiro" uniqKey="Kato N" first="Norihiro" last="Kato">Norihiro Kato</name><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S" last="Kooner">Jaspal S. Kooner</name><name sortKey="Kotea, Navaratnam" sort="Kotea, Navaratnam" uniqKey="Kotea N" first="Navaratnam" last="Kotea">Navaratnam Kotea</name><name sortKey="Kowlessur, Sudhir" sort="Kowlessur, Sudhir" uniqKey="Kowlessur S" first="Sudhir" last="Kowlessur">Sudhir Kowlessur</name><name sortKey="Kriebel, Jennifer" sort="Kriebel, Jennifer" uniqKey="Kriebel J" first="Jennifer" last="Kriebel">Jennifer Kriebel</name><name sortKey="Kyrtopoulos, Soterios A" sort="Kyrtopoulos, Soterios A" uniqKey="Kyrtopoulos S" first="Soterios A" last="Kyrtopoulos">Soterios A. Kyrtopoulos</name><name sortKey="Lehne, Benjamin" sort="Lehne, Benjamin" uniqKey="Lehne B" first="Benjamin" last="Lehne">Benjamin Lehne</name><name sortKey="Loh, Marie" sort="Loh, Marie" uniqKey="Loh M" first="Marie" last="Loh">Marie Loh</name><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name><name sortKey="Mok, Zuan Yu" sort="Mok, Zuan Yu" uniqKey="Mok Z" first="Zuan Yu" last="Mok">Zuan Yu Mok</name><name sortKey="Motta, Valeria" sort="Motta, Valeria" uniqKey="Motta V" first="Valeria" last="Motta">Valeria Motta</name><name sortKey="Ng, Hong Kiat" sort="Ng, Hong Kiat" uniqKey="Ng H" first="Hong Kiat" last="Ng">Hong Kiat Ng</name><name sortKey="Pattou, Francois" sort="Pattou, Francois" uniqKey="Pattou F" first="François" last="Pattou">François Pattou</name><name sortKey="Pitk Niemi, Janne" sort="Pitk Niemi, Janne" uniqKey="Pitk Niemi J" first="Janne" last="Pitk Niemi">Janne Pitk Niemi</name><name sortKey="Prokisch, Holger" sort="Prokisch, Holger" uniqKey="Prokisch H" first="Holger" last="Prokisch">Holger Prokisch</name><name sortKey="Punjabi, Prakash" sort="Punjabi, Prakash" uniqKey="Punjabi P" first="Prakash" last="Punjabi">Prakash Punjabi</name><name sortKey="Relton, Caroline L" sort="Relton, Caroline L" uniqKey="Relton C" first="Caroline L" last="Relton">Caroline L. Relton</name><name sortKey="Richmond, Rebecca C" sort="Richmond, Rebecca C" uniqKey="Richmond R" first="Rebecca C" last="Richmond">Rebecca C. Richmond</name><name sortKey="Rota, Federica" sort="Rota, Federica" uniqKey="Rota F" first="Federica" last="Rota">Federica Rota</name><name sortKey="Rozario, Michelle Ann" sort="Rozario, Michelle Ann" uniqKey="Rozario M" first="Michelle Ann" last="Rozario">Michelle Ann Rozario</name><name sortKey="Saleheen, Danish" sort="Saleheen, Danish" uniqKey="Saleheen D" first="Danish" last="Saleheen">Danish Saleheen</name><name sortKey="Schafmayer, Clemens" sort="Schafmayer, Clemens" uniqKey="Schafmayer C" first="Clemens" last="Schafmayer">Clemens Schafmayer</name><name sortKey="Scott, James" sort="Scott, James" uniqKey="Scott J" first="James" last="Scott">James Scott</name><name sortKey="Scott, William R" sort="Scott, William R" uniqKey="Scott W" first="William R" last="Scott">William R. Scott</name><name sortKey="Soininen, Pasi" sort="Soininen, Pasi" uniqKey="Soininen P" first="Pasi" last="Soininen">Pasi Soininen</name><name sortKey="Soong, Richie" sort="Soong, Richie" uniqKey="Soong R" first="Richie" last="Soong">Richie Soong</name><name sortKey="Tai, E Shyong" sort="Tai, E Shyong" uniqKey="Tai E" first="E-Shyong" last="Tai">E-Shyong Tai</name><name sortKey="Tan, Sian Tsung" sort="Tan, Sian Tsung" uniqKey="Tan S" first="Sian-Tsung" last="Tan">Sian-Tsung Tan</name><name sortKey="Tarantini, Letizia" sort="Tarantini, Letizia" uniqKey="Tarantini L" first="Letizia" last="Tarantini">Letizia Tarantini</name><name sortKey="Thorand, Barbara" sort="Thorand, Barbara" uniqKey="Thorand B" first="Barbara" last="Thorand">Barbara Thorand</name><name sortKey="Tuomilehto, Jaakko" sort="Tuomilehto, Jaakko" uniqKey="Tuomilehto J" first="Jaakko" last="Tuomilehto">Jaakko Tuomilehto</name><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name><name sortKey="Wahl, Simone" sort="Wahl, Simone" uniqKey="Wahl S" first="Simone" last="Wahl">Simone Wahl</name><name sortKey="Wickremasinghe, Ananda Rajitha" sort="Wickremasinghe, Ananda Rajitha" uniqKey="Wickremasinghe A" first="Ananda Rajitha" last="Wickremasinghe">Ananda Rajitha Wickremasinghe</name><name sortKey="Yengo, Loic" sort="Yengo, Loic" uniqKey="Yengo L" first="Loic" last="Yengo">Loic Yengo</name><name sortKey="Zhang, Weihua" sort="Zhang, Weihua" uniqKey="Zhang W" first="Weihua" last="Zhang">Weihua Zhang</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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