Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

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de Vries, Paul S.University of Texas (author)

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Article/chapterEnglish2019

Publisher, publication year, extent ...

2019-01-29
Oxford University Press,2019
printrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-161740
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-161740URI
https://doi.org/10.1093/aje/kwz005DOI
https://lup.lub.lu.se/record/214a185e-d344-42e1-8185-4c5840429109URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:141294981URI

Supplementary language notes

Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Hälsovetenskap Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Health Sciences Public Health, Global Health, Social Medicine and Epidemiology hsv//eng
alcohol consumption
cholesterol
gene-environment interactions
gene-lifestyle interactions
genome-wide association studies
lipids
triglycerides
alcohol consumption
cholesterol
gene-environment interactions
gene-lifestyle interactions
genome-wide association studies
lipids
triglycerides

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Brown, Michael R. (author)
Bentley, Amy R. (author)
Sung, Yun J. (author)
Winkler, Thomas W. (author)
Ntalla, Ioanna (author)
Schwander, Karen (author)
Kraja, Aldi T. (author)
Guo, Xiuqing (author)
Franceschini, Nora (author)
Cheng, Ching-Yu (author)
Sim, Xueling (author)
Vojinovic, Dina (author)
Huffman, Jennifer E. (author)
Musani, Solomon K. (author)
Li, Changwei (author)
Feitosa, Mary F. (author)
Richard, Melissa A. (author)
Noordam, Raymond (author)
Aschard, Hugues (author)
Bartz, Traci M. (author)
Bielak, Lawrence F. (author)
Deng, Xuan (author)
Dorajoo, Rajkumar (author)
Lohman, Kurt K. (author)
Manning, Alisa K. (author)
Rankinen, Tuomo (author)
Smith, Albert V. (author)
Tajuddin, Salman M. (author)
Evangelou, EvangelosKarolinska Institutet (author)
Graff, Mariaelisa (author)
Alver, Maris (author)
Boissel, Mathilde (author)
Chai, Jin Fang (author)
Chen, XuKarolinska Institutet (author)
Divers, Jasmin (author)
Gandin, Ilaria (author)
Gao, Chuan (author)
Goel, Anuj (author)
Hagemeijer, Yanick (author)
Harris, Sarah E. (author)
Hartwig, Fernando P. (author)
He, Meian (author)
Horimoto, Andrea R. V. R. (author)
Hsu, Fang-Chi (author)
Jackson, Anne U. (author)
Kasturiratne, Anuradhani (author)
Komulainen, Pirjo (author)
Kuehnel, Brigitte (author)
Laguzzi, FedericaKarolinska Institutet (author)
Lee, Joseph H. (author)
Luan, Jian'an (author)
Lyytikainen, Leo-Pekka (author)
Matoba, Nana (author)
Nolte, Ilja M. (author)
Pietzner, Maik (author)
Riaz, Muhammad (author)
Said, M. Abdullah (author)
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Sofer, Tamar (author)
Stancakova, Alena (author)
Takeuchi, Fumihiko (author)
Tayo, Bamidele O. (author)
van der Most, Peter J. (author)
V. Varga, TiborLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-tv_ (author)
Wang, Yajuan (author)
Ware, Erin B. (author)
Wen, Wanqing (author)
Yanek, Lisa R. (author)
Zhang, Weihua (author)
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Canouil, Mickael (author)
Charumathi, Sabanayagam (author)
Chen, Yii-Der Ida (author)
Connell, John M. (author)
de Faire, UlfKarolinska Institutet (author)
de las Fuentes, Lisa (author)
de Mutsert, Renee (author)
de Silva, H. Janaka (author)
Ding, Jingzhong (author)
Dominiczak, Anna F. (author)
Duan, Qing (author)
Eaton, Charles B. (author)
Eppinga, Ruben N. (author)
Faul, Jessica D. (author)
Fisher, Virginia (author)
Forrester, Terrence (author)
Franco, Oscar H. (author)
Friedlander, Yechiel (author)
Ghanbari, Mohsen (author)
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Gu, C. Charles (author)
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Jacobs, David R., Jr. (author)
Johnson, Craig (author)
Jonas, Jost Bruno (author)
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Kooperberg, Charles (author)
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Manichaikul, Ani W. (author)
McKenzie, Colin A. (author)
Meitinger, Thomas (author)
Metspalu, Andres (author)
Milaneschi, Yuri (author)
Milani, Lili (author)
Mohlke, Karen L.Karolinska Institutet (author)
Mosley, Thomas H., Jr. (author)
Mukamal, Kenneth J. (author)
Nalls, Mike A. (author)
Nauck, Matthias (author)
Nelson, Christopher P. (author)
Sotoodehnia, Nona (author)
O'Connell, Jeff R. (author)
Palmer, Nicholette D. (author)
Pazoki, Raha (author)
Pedersen, Nancy L.Karolinska Institutet (author)
Peters, Annette (author)
Peyser, Patricia A. (author)
Polasek, Ozren (author)
Poulter, Neil (author)
Raffel, Leslie J. (author)
Raitakari, Olli T. (author)
Reiner, Alex P. (author)
Rice, Treva K. (author)
Rich, Stephen S. (author)
Robino, Antonietta (author)
Robinson, Jennifer G. (author)
Rose, Lynda M. (author)
Rudan, Igor (author)
Schmidt, Carsten O. (author)
Schreiner, Pamela J. (author)
Scott, William R. (author)
Sever, Peter (author)
Shi, Yuan (author)
Sidney, Stephen (author)
Sims, Mario (author)
Smith, Blair H. (author)
Smith, Jennifer A. (author)
Snieder, Harold (author)
Starr, John M. (author)
Strauch, Konstantin (author)
Tan, Nicholas (author)
Taylor, Kent D. (author)
Teo, Yik Ying (author)
Tham, Yih Chung (author)
Uitterlinden, Andre G. (author)
van Heemst, Diana (author)
Vuckovic, Dragana (author)
Waldenberger, Melanie (author)
Wang, Lihua (author)
Wang, Yujie (author)
Wang, Zhe (author)
Wei, Wen Bin (author)
Williams, Christine (author)
Wilson, Gregory, Sr. (author)
Wojczynski, Mary K. (author)
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Yu, Bing (author)
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Yuan, Jian-Min (author)
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Becker, Diane M. (author)
Boehnke, Michael (author)
Bowden, Donald W. (author)
Chambers, John C. (author)
Deary, Ian J. (author)
Esko, Tonu (author)
Farrall, Martin (author)
Franks, Paul W.Umeå University,Lund University,Lunds universitet,Umeå universitet,Avdelningen för medicin,Department of Nutrition, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, United Kingdom,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf (author)
Freedman, Barry I. (author)
Froguel, Philippe (author)
Gasparini, Paolo (author)
Gieger, Christian (author)
Horta, Bernardo L. (author)
Kamatani, Yoichiro (author)
Kato, Norihiro (author)
Kooner, Jaspal S. (author)
Laakso, Markku (author)
Leander, Karin (author)
Lehtimaki, Terho (author)
Magnusson, Patrik K. E. (author)
Penninx, Brenda (author)
Pereira, Alexandre C. (author)
Rauramaa, Rainer (author)
Samani, Nilesh J. (author)
Scott, James (author)
Shu, Xiao-Ou (author)
van der Harst, Pim (author)
Wagenknecht, Lynne E. (author)
Wang, Ya Xing (author)
Wareham, Nicholas J. (author)
Watkins, Hugh (author)
Weir, David R. (author)
Wickremasinghe, Ananda R. (author)
Zheng, Wei (author)
Elliott, Paul (author)
North, Kari E. (author)
Bouchard, Claude (author)
Evans, Michele K. (author)
Gudnason, Vilmundur (author)
Liu, Ching-Ti (author)
Liu, Yongmei (author)
Psaty, Bruce M. (author)
Ridker, Paul M. (author)
van Dam, Rob M. (author)
Kardia, Sharon L. R. (author)
Zhu, Xiaofeng (author)
Rotimi, Charles N. (author)
Mook-Kanamori, Dennis O. (author)
Fornage, Myriam (author)
Kelly, Tanika N. (author)
Fox, Ervin R. (author)
Hayward, Caroline (author)
van Duijn, Cornelia M. (author)
Tai, E. Shyong (author)
Wong, Tien Yin (author)
Liu, Jingmin (author)
Rotter, Jerome I. (author)
Gauderman, W. James (author)
Province, Michael A. (author)
Munroe, Patricia B. (author)
Rice, Kenneth (author)
Chasman, Daniel I. (author)
Cupples, L. Adrienne (author)
Rao, Dabeeru C. (author)
Morrison, Alanna C.University of Texas (author)
Karolinska InstitutetUniversity of Texas (creator_code:org_t)
et al.

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In:American Journal of Epidemiology: Oxford University Press188:6, s. 1033-10540002-92621476-6256

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By the author/editor: de Vries, Paul S ...; Brown, Michael R ...; Bentley, Amy R.; Sung, Yun J.; Winkler, Thomas ...; Ntalla, Ioanna; show more...; Schwander, Karen; Kraja, Aldi T.; Guo, Xiuqing; Franceschini, No ...; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Huffman, Jennife ...; Musani, Solomon ...; Li, Changwei; Feitosa, Mary F.; Richard, Melissa ...; Noordam, Raymond; Aschard, Hugues; Bartz, Traci M.; Bielak, Lawrence ...; Deng, Xuan; Dorajoo, Rajkuma ...; Lohman, Kurt K.; Manning, Alisa K ...; Rankinen, Tuomo; Smith, Albert V.; Tajuddin, Salman ...; Evangelou, Evang ...; Graff, Mariaelis ...; Alver, Maris; Boissel, Mathild ...; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gandin, Ilaria; Gao, Chuan; Goel, Anuj; Hagemeijer, Yani ...; Harris, Sarah E.; Hartwig, Fernand ...; He, Meian; Horimoto, Andrea ...; Hsu, Fang-Chi; Jackson, Anne U.; Kasturiratne, An ...; Komulainen, Pirj ...; Kuehnel, Brigitt ...; Laguzzi, Federic ...; Lee, Joseph H.; Luan, Jian'an; Lyytikainen, Leo ...; Matoba, Nana; Nolte, Ilja M.; Pietzner, Maik; Riaz, Muhammad; Said, M. Abdulla ...; Scott, Robert A.; Sofer, Tamar; Stancakova, Alen ...; Takeuchi, Fumihi ...; Tayo, Bamidele O ...; van der Most, Pe ...; V. Varga, Tibor; Wang, Yajuan; Ware, Erin B.; Wen, Wanqing; Yanek, Lisa R.; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Amin, Najaf; Amini, Marzyeh; Arking, Dan E.; Aung, Tin; Ballantyne, Chri ...; Boerwinkle, Eric; Broeckel, Ulrich; Campbell, Archie; Canouil, Mickael; Charumathi, Saba ...; Chen, Yii-Der Id ...; Connell, John M.; de Faire, Ulf; de las Fuentes, ...; de Mutsert, Rene ...; de Silva, H. Jan ...; Ding, Jingzhong; Dominiczak, Anna ...; Duan, Qing; Eaton, Charles B ...; Eppinga, Ruben N ...; Faul, Jessica D.; Fisher, Virginia; Forrester, Terre ...; Franco, Oscar H.; Friedlander, Yec ...; Ghanbari, Mohsen; Giulianini, Fran ...; Grabe, Hans J.; Grove, Megan L.; Gu, C. Charles; Harris, Tamara B ...; Heikkinen, Sami; Heng, Chew-Kiat; Hirata, Makoto; Hixson, James E.; Howard, Barbara ...; Ikram, M. Arfan; Jacobs, David R. ...; Johnson, Craig; Jonas, Jost Brun ...; Kammerer, Candac ...; Katsuya, Tomohir ...; Khor, Chiea Chue ...; Kilpelainen, Tuo ...; Koh, Woon-Puay; Koistinen, Heikk ...; Kolcic, Ivana; Kooperberg, Char ...; Krieger, Jose E.; Kritchevsky, Ste ...; Kubo, Michiaki; Kuusisto, Johann ...; Lakka, Timo A.; Langefeld, Carl ...; Langenberg, Clau ...; Launer, Lenore J ...; Lehne, Benjamin; Lemaitre, Rozenn ...; Li, Yize; Liang, Jingjing; Liu, Jianjun; Liu, Kiang; Loh, Marie; Louie, Tin; Magi, Reedik; Manichaikul, Ani ...; McKenzie, Colin ...; Meitinger, Thoma ...; Metspalu, Andres; Milaneschi, Yuri; Milani, Lili; Mohlke, Karen L.; Mosley, Thomas H ...; Mukamal, Kenneth ...; Nalls, Mike A.; Nauck, Matthias; Nelson, Christop ...; Sotoodehnia, Non ...; O'Connell, Jeff ...; Palmer, Nicholet ...; Pazoki, Raha; Pedersen, Nancy ...; Peters, Annette; Peyser, Patricia ...; Polasek, Ozren; Poulter, Neil; Raffel, Leslie J ...; Raitakari, Olli ...; Reiner, Alex P.; Rice, Treva K.; Rich, Stephen S.; Robino, Antoniet ...; Robinson, Jennif ...; Rose, Lynda M.; Rudan, Igor; Schmidt, Carsten ...; Schreiner, Pamel ...; Scott, William R ...; Sever, Peter; Shi, Yuan; Sidney, Stephen; Sims, Mario; Smith, Blair H.; Smith, Jennifer ...; Snieder, Harold; Starr, John M.; Strauch, Konstan ...; Tan, Nicholas; Taylor, Kent D.; Teo, Yik Ying; Tham, Yih Chung; Uitterlinden, An ...; van Heemst, Dian ...; Vuckovic, Dragan ...; Waldenberger, Me ...; Wang, Lihua; Wang, Yujie; Wang, Zhe; Wei, Wen Bin; Williams, Christ ...; Wilson, Gregory, ...; Wojczynski, Mary ...; Yao, Jie; Yu, Bing; Yu, Caizheng; Yuan, Jian-Min; Zhao, Wei; Zonderman, Alan ...; Becker, Diane M.; Boehnke, Michael; Bowden, Donald W ...; Chambers, John C ...; Deary, Ian J.; Esko, Tonu; Farrall, Martin; Franks, Paul W.; Freedman, Barry ...; Froguel, Philipp ...; Gasparini, Paolo; Gieger, Christia ...; Horta, Bernardo ...; Kamatani, Yoichi ...; Kato, Norihiro; Kooner, Jaspal S ...; Laakso, Markku; Leander, Karin; Lehtimaki, Terho; Magnusson, Patri ...; Penninx, Brenda; Pereira, Alexand ...; Rauramaa, Rainer; Samani, Nilesh J ...; Scott, James; Shu, Xiao-Ou; van der Harst, P ...; Wagenknecht, Lyn ...; Wang, Ya Xing; Wareham, Nichola ...; Watkins, Hugh; Weir, David R.; Wickremasinghe, ...; Zheng, Wei; Elliott, Paul; North, Kari E.; Bouchard, Claude; Evans, Michele K ...; Gudnason, Vilmun ...; Liu, Ching-Ti; Liu, Yongmei; Psaty, Bruce M.; Ridker, Paul M.; van Dam, Rob M.; Kardia, Sharon L ...; Zhu, Xiaofeng; Rotimi, Charles ...; Mook-Kanamori, D ...; Fornage, Myriam; Kelly, Tanika N.; Fox, Ervin R.; Hayward, Carolin ...; van Duijn, Corne ...; Tai, E. Shyong; Wong, Tien Yin; Liu, Jingmin; Rotter, Jerome I ...; Gauderman, W. Ja ...; Province, Michae ...; Munroe, Patricia ...; Rice, Kenneth; Chasman, Daniel ...; Cupples, L. Adri ...; Rao, Dabeeru C.; Morrison, Alanna ...; show less...

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