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1. Associations of genetically determined lipid traits and lipid-modifying agents with the risk of diabetic retinopathy: A Mendelian randomization study

Author: Li, Ning, Zhang, Xiaoyu, Zhang, Meng, Wu, Lijuan, Li, Changwei, Pan, Yuesong, Wang, Wei, Ji, Jianguang, Zheng, Deqiang, Li, Ning, Zhang, Xiaoyu, Zhang, Meng, Wu, Lijuan, Li, Changwei, Pan, Yuesong, Wang, Wei, Ji, Jianguang, and Zheng, Deqiang
Abstract: Background and aims: The evidence that dyslipidemia is associated with hyperglycemia calls for an investigation of whether dyslipidemia, as well as lipid-modifying agents, could affect the subsequent development of diabetic retinopathy (DR). Therefore, we aimed to address these unanswered questions by utilizing Mendelian randomization (MR) analysis. Methods: Genetic variants were selected from the UK Biobank as instruments to serve as proxies for lipid traits [high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB)]. Univariable and multivariable MR analyses were performed to examine the associations of these lipid traits with DR and different levels of severity of DR. Based on the evidence for the effects of lipids on outcomes, we estimated the causal relevance of cholesteryl ester transfer protein (CETP) inhibitors in severe nonproliferative and proliferative DR using protein quantitative trait loci (pQTLs) and expression quantitative trait loci (eQTLs) as instruments. Results: Genetically determined HDL-C levels were inversely associated with the risk of severe nonproliferative DR (OR = 0.70, 95% CI = 0.52–0.94) and proliferative DR (OR = 0.90, 95% CI = 0.83–0.97) in the main analyses utilizing the inverse variance-weighted (IVW) MR method and a couple of sensitivity analyses. No association was noted between genetically proxied CETP inhibitors and DR. Conclusions: This MR study suggests the casual protective roles of HDL-C in severe nonproliferative DR and proliferative DR, which calls for further studies to confirm these findings. Current lipid-modifying agents acting on HDL-C may not reduce the risk of DR and new treatments are required in the future.
Published: 2023

2. Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study.

Author: Wang, Yuxuan, Wang, Yuxuan, Selvaraj, Margaret, Li, Xihao, Li, Zilin, Holdcraft, Jacob, Arnett, Donna, Bis, Joshua, Blangero, John, Boerwinkle, Eric, Bowden, Donald, Cade, Brian, Carlson, Jenna, Carson, April, Chen, Yii-Der, Curran, Joanne, de Vries, Paul, Dutcher, Susan, Ellinor, Patrick, Floyd, James, Fornage, Myriam, Freedman, Barry, Gabriel, Stacey, Germer, Soren, Gibbs, Richard, Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite, Joehanes, Roby, Kaplan, Robert, Kardia, Sharon, Kelly, Tanika, Kim, Ryan, Kooperberg, Charles, Kral, Brian, Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth, Mahaney, Michael, Martin, Lisa, Mathias, Rasika, Minster, Ryan, Mitchell, Braxton, Montasser, May, Morrison, Alanna, Murabito, Joanne, Naseri, Take, OConnell, Jeffrey, Palmer, Nicholette, Preuss, Michael, Psaty, Bruce, Raffield, Laura, Rao, Dabeeru, Redline, Susan, Reiner, Alexander, Rich, Stephen, Ruepena, Muagututia, Sheu, Wayne, Smith, Jennifer, Smith, Albert, Tiwari, Hemant, Tsai, Michael, Viaud-Martinez, Karine, Wang, Zhe, Yanek, Lisa, Zhao, Wei, Lin, Xihong, Natarajan, Pradeep, Peloso, Gina, Rotter, Jerome, Wang, Yuxuan, Wang, Yuxuan, Selvaraj, Margaret, Li, Xihao, Li, Zilin, Holdcraft, Jacob, Arnett, Donna, Bis, Joshua, Blangero, John, Boerwinkle, Eric, Bowden, Donald, Cade, Brian, Carlson, Jenna, Carson, April, Chen, Yii-Der, Curran, Joanne, de Vries, Paul, Dutcher, Susan, Ellinor, Patrick, Floyd, James, Fornage, Myriam, Freedman, Barry, Gabriel, Stacey, Germer, Soren, Gibbs, Richard, Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite, Joehanes, Roby, Kaplan, Robert, Kardia, Sharon, Kelly, Tanika, Kim, Ryan, Kooperberg, Charles, Kral, Brian, Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth, Mahaney, Michael, Martin, Lisa, Mathias, Rasika, Minster, Ryan, Mitchell, Braxton, Montasser, May, Morrison, Alanna, Murabito, Joanne, Naseri, Take, OConnell, Jeffrey, Palmer, Nicholette, Preuss, Michael, Psaty, Bruce, Raffield, Laura, Rao, Dabeeru, Redline, Susan, Reiner, Alexander, Rich, Stephen, Ruepena, Muagututia, Sheu, Wayne, Smith, Jennifer, Smith, Albert, Tiwari, Hemant, Tsai, Michael, Viaud-Martinez, Karine, Wang, Zhe, Yanek, Lisa, Zhao, Wei, Lin, Xihong, Natarajan, Pradeep, Peloso, Gina, and Rotter, Jerome
Abstract: Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.
Published: 2023

3. A statistical framework for powerful multi-trait rare variant analysis in large-scale whole-genome sequencing studies

Author: Li, Xihao, Chen, Han, Selvaraj, Margaret Sunitha, Van Buren, Eric, Zhou, Hufeng, Wang, Yuxuan, Sun, Ryan, McCaw, Zachary R, Yu, Zhi, Arnett, Donna K, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Carson, April P, Carlson, Jenna C, Chami, Nathalie, Chen, Yii-Der Ida, Curran, Joanne E, de Vries, Paul S, Fornage, Myriam, Franceschini, Nora, Freedman, Barry I, Gu, Charles, Heard-Costa, Nancy L, He, Jiang, Hou, Lifang, Hung, Yi-Jen, Irvin, Marguerite R, Kaplan, Robert C, Kardia, Sharon L R, Kelly, Tanika, Konigsberg, Iain, Kooperberg, Charles, Kral, Brian G, Li, Changwei, Loos, Ruth J F, Mahaney, Michael C, Martin, Lisa W, Mathias, Rasika A, Minster, Ryan L, Mitchell, Braxton D, Montasser, May E, Morrison, Alanna C, Palmer, Nicholette D, Peyser, Patricia A, Psaty, Bruce M, Raffield, Laura M, Li, Xihao, Chen, Han, Selvaraj, Margaret Sunitha, Van Buren, Eric, Zhou, Hufeng, Wang, Yuxuan, Sun, Ryan, McCaw, Zachary R, Yu, Zhi, Arnett, Donna K, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Carson, April P, Carlson, Jenna C, Chami, Nathalie, Chen, Yii-Der Ida, Curran, Joanne E, de Vries, Paul S, Fornage, Myriam, Franceschini, Nora, Freedman, Barry I, Gu, Charles, Heard-Costa, Nancy L, He, Jiang, Hou, Lifang, Hung, Yi-Jen, Irvin, Marguerite R, Kaplan, Robert C, Kardia, Sharon L R, Kelly, Tanika, Konigsberg, Iain, Kooperberg, Charles, Kral, Brian G, Li, Changwei, Loos, Ruth J F, Mahaney, Michael C, Martin, Lisa W, Mathias, Rasika A, Minster, Ryan L, Mitchell, Braxton D, Montasser, May E, Morrison, Alanna C, Palmer, Nicholette D, Peyser, Patricia A, Psaty, Bruce M, and Raffield, Laura M
Abstract: Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally-scalable analytical pipeline for functionally-informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in 61,861 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered new associations with lipid traits missed by single-trait analysis, including rare variants within an enhancer of NIPSNAP3A and an intergenic region on chromosome 1.
Published: 2023

4. Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

Author: Wang, Yuxuan, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Holdcraft, Jacob A., Arnett, Donna K., Bis, Joshua C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Cade, Brian E., Carlson, Jenna C., Carson, April P., Chen, Yii Der Ida, Curran, Joanne E., de Vries, Paul S., Dutcher, Susan K., Ellinor, Patrick T., Floyd, James S., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite R., Joehanes, Roby, Kaplan, Robert C., Kardia, Sharon LR, Kelly, Tanika N., Kim, Ryan, Kooperberg, Charles, Kral, Brian G., Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth J.F., Mahaney, Michael C., Martin, Lisa W., Mathias, Rasika A., Minster, Ryan L., Mitchell, Braxton D., Montasser, May E., Morrison, Alanna C., Murabito, Joanne M., Wang, Yuxuan, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Holdcraft, Jacob A., Arnett, Donna K., Bis, Joshua C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Cade, Brian E., Carlson, Jenna C., Carson, April P., Chen, Yii Der Ida, Curran, Joanne E., de Vries, Paul S., Dutcher, Susan K., Ellinor, Patrick T., Floyd, James S., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite R., Joehanes, Roby, Kaplan, Robert C., Kardia, Sharon LR, Kelly, Tanika N., Kim, Ryan, Kooperberg, Charles, Kral, Brian G., Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth J.F., Mahaney, Michael C., Martin, Lisa W., Mathias, Rasika A., Minster, Ryan L., Mitchell, Braxton D., Montasser, May E., Morrison, Alanna C., and Murabito, Joanne M.
Abstract: Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.
Published: 2023

5. A statistical framework for powerful multi-trait rare variant analysis in large-scale whole-genome sequencing studies

Author: Li, Xihao, Chen, Han, Selvaraj, Margaret Sunitha, Van Buren, Eric, Zhou, Hufeng, Wang, Yuxuan, Sun, Ryan, McCaw, Zachary R, Yu, Zhi, Arnett, Donna K, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Carson, April P, Carlson, Jenna C, Chami, Nathalie, Chen, Yii-Der Ida, Curran, Joanne E, de Vries, Paul S, Fornage, Myriam, Franceschini, Nora, Freedman, Barry I, Gu, Charles, Heard-Costa, Nancy L, He, Jiang, Hou, Lifang, Hung, Yi-Jen, Irvin, Marguerite R, Kaplan, Robert C, Kardia, Sharon L R, Kelly, Tanika, Konigsberg, Iain, Kooperberg, Charles, Kral, Brian G, Li, Changwei, Loos, Ruth J F, Mahaney, Michael C, Martin, Lisa W, Mathias, Rasika A, Minster, Ryan L, Mitchell, Braxton D, Montasser, May E, Morrison, Alanna C, Palmer, Nicholette D, Peyser, Patricia A, Psaty, Bruce M, Raffield, Laura M, Li, Xihao, Chen, Han, Selvaraj, Margaret Sunitha, Van Buren, Eric, Zhou, Hufeng, Wang, Yuxuan, Sun, Ryan, McCaw, Zachary R, Yu, Zhi, Arnett, Donna K, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Carson, April P, Carlson, Jenna C, Chami, Nathalie, Chen, Yii-Der Ida, Curran, Joanne E, de Vries, Paul S, Fornage, Myriam, Franceschini, Nora, Freedman, Barry I, Gu, Charles, Heard-Costa, Nancy L, He, Jiang, Hou, Lifang, Hung, Yi-Jen, Irvin, Marguerite R, Kaplan, Robert C, Kardia, Sharon L R, Kelly, Tanika, Konigsberg, Iain, Kooperberg, Charles, Kral, Brian G, Li, Changwei, Loos, Ruth J F, Mahaney, Michael C, Martin, Lisa W, Mathias, Rasika A, Minster, Ryan L, Mitchell, Braxton D, Montasser, May E, Morrison, Alanna C, Palmer, Nicholette D, Peyser, Patricia A, Psaty, Bruce M, and Raffield, Laura M
Abstract: Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally-scalable analytical pipeline for functionally-informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in 61,861 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered new associations with lipid traits missed by single-trait analysis, including rare variants within an enhancer of NIPSNAP3A and an intergenic region on chromosome 1.
Published: 2023

6. Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

Author: Wang, Yuxuan, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Holdcraft, Jacob A., Arnett, Donna K., Bis, Joshua C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Cade, Brian E., Carlson, Jenna C., Carson, April P., Chen, Yii Der Ida, Curran, Joanne E., de Vries, Paul S., Dutcher, Susan K., Ellinor, Patrick T., Floyd, James S., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite R., Joehanes, Roby, Kaplan, Robert C., Kardia, Sharon LR, Kelly, Tanika N., Kim, Ryan, Kooperberg, Charles, Kral, Brian G., Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth J.F., Mahaney, Michael C., Martin, Lisa W., Mathias, Rasika A., Minster, Ryan L., Mitchell, Braxton D., Montasser, May E., Morrison, Alanna C., Murabito, Joanne M., Wang, Yuxuan, Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Holdcraft, Jacob A., Arnett, Donna K., Bis, Joshua C., Blangero, John, Boerwinkle, Eric, Bowden, Donald W., Cade, Brian E., Carlson, Jenna C., Carson, April P., Chen, Yii Der Ida, Curran, Joanne E., de Vries, Paul S., Dutcher, Susan K., Ellinor, Patrick T., Floyd, James S., Fornage, Myriam, Freedman, Barry I., Gabriel, Stacey, Germer, Soren, Gibbs, Richard A., Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy, Hildalgo, Bertha, Hou, Lifang, Irvin, Marguerite R., Joehanes, Roby, Kaplan, Robert C., Kardia, Sharon LR, Kelly, Tanika N., Kim, Ryan, Kooperberg, Charles, Kral, Brian G., Levy, Daniel, Li, Changwei, Liu, Chunyu, Lloyd-Jone, Don, Loos, Ruth J.F., Mahaney, Michael C., Martin, Lisa W., Mathias, Rasika A., Minster, Ryan L., Mitchell, Braxton D., Montasser, May E., Morrison, Alanna C., and Murabito, Joanne M.
Abstract: Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.
Published: 2023

7. Development and Validation of a Two-Step Predictive Risk Stratification Model for Coronavirus Disease 2019 In-hospital Mortality: A Multicenter Retrospective Cohort Study.

Author: Li, Yang, Li, Yang, Kong, Yanlei, Ebell, Mark, Martinez, Leonardo, Cai, Xinyan, Lennon, Robert, Tarn, Derjung, Mainous, Arch, Zgierska, Aleksandra, Barrett, Bruce, Tuan, Wen-Jan, Maloy, Kevin, Goyal, Munish, Krist, Alex, Gal, Tamas, Sung, Meng-Hsuan, Li, Changwei, Jin, Yier, Shen, Ye, Li, Yang, Li, Yang, Kong, Yanlei, Ebell, Mark, Martinez, Leonardo, Cai, Xinyan, Lennon, Robert, Tarn, Derjung, Mainous, Arch, Zgierska, Aleksandra, Barrett, Bruce, Tuan, Wen-Jan, Maloy, Kevin, Goyal, Munish, Krist, Alex, Gal, Tamas, Sung, Meng-Hsuan, Li, Changwei, Jin, Yier, and Shen, Ye
Abstract: OBJECTIVES: An accurate prognostic score to predict mortality for adults with COVID-19 infection is needed to understand who would benefit most from hospitalizations and more intensive support and care. We aimed to develop and validate a two-step score system for patient triage, and to identify patients at a relatively low level of mortality risk using easy-to-collect individual information. DESIGN: Multicenter retrospective observational cohort study. SETTING: Four health centers from Virginia Commonwealth University, Georgetown University, the University of Florida, and the University of California, Los Angeles. PATIENTS: Coronavirus Disease 2019-confirmed and hospitalized adult patients. MEASUREMENTS AND MAIN RESULTS: We included 1,673 participants from Virginia Commonwealth University (VCU) as the derivation cohort. Risk factors for in-hospital death were identified using a multivariable logistic model with variable selection procedures after repeated missing data imputation. A two-step risk score was developed to identify patients at lower, moderate, and higher mortality risk. The first step selected increasing age, more than one pre-existing comorbidities, heart rate >100 beats/min, respiratory rate ≥30 breaths/min, and SpO2 <93% into the predictive model. Besides age and SpO2, the second step used blood urea nitrogen, absolute neutrophil count, C-reactive protein, platelet count, and neutrophil-to-lymphocyte ratio as predictors. C-statistics reflected very good discrimination with internal validation at VCU (0.83, 95% CI 0.79-0.88) and external validation at the other three health systems (range, 0.79-0.85). A one-step model was also derived for comparison. Overall, the two-step risk score had better performance than the one-step score. CONCLUSIONS: The two-step scoring system used widely available, point-of-care data for triage of COVID-19 patients and is a potentially time- and cost-saving tool in practice.
Published: 2022

8. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Author: de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, Kavousi, Maryam, de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, and Kavousi, Maryam
Abstract: Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Published: 2021

9. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Author: de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, Kavousi, Maryam, de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, and Kavousi, Maryam
Abstract: Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Published: 2021

10. Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus among Chinese: The Beijing longitudinal study of aging

Author: Cao, Xue, Tang, Zhe, Zhang, Jie, Li, Haibin, Singh, Manjot, Sun, Fei, Li, Xiaochun, Li, Changwei, Wang, Youxin, Guo, Xiuhua, Zheng, Deqiang, Cao, Xue, Tang, Zhe, Zhang, Jie, Li, Haibin, Singh, Manjot, Sun, Fei, Li, Xiaochun, Li, Changwei, Wang, Youxin, Guo, Xiuhua, and Zheng, Deqiang
Abstract: Background: Some previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration. Methods: In total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables. Results: Over the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62–1.55), 0.48 (95% CI: 0.27–0.85) and 0.44 (95% CI: 0.25–0.80) for individuals with HDL-C levels within the 1.15–1.39, 1.40–1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels < 1.15 mmol/L. Multiple sensitivity analyses similarly revealed reduced risk of diabetes incidence with increased HDL-C levels. Incorporating the levels of HDL-C into a multivariate model significantly enhanced the overall power of the predictive model (P values were 0.0296, 0.0011, respectively, for 5- and 10-year risk of diabetes). Conclusions: Levels of HDL-C were independently and negatively associated with the risk of the new-onset T2DM among
Published: 2021

11. Prevalence of Abdominal Obesity in Chinese Middle-Aged and Older Adults with a Normal Body Mass Index and Its Association with Type 2 Diabetes Mellitus: A Nationally Representative Cohort Study from 2011 to 2018

Author: Chen, Xuan, Duan, Mingrui, Hou, Rui, Zheng, Manqi, Li, Haibin, Singh, Manjot, Li, Changwei, Liu, Kuo, Zhang, Feng, Yang, Xinghua, Luo, Yanxia, He, Yan, Wu, Lijuan, Zheng, Deqiang, Chen, Xuan, Duan, Mingrui, Hou, Rui, Zheng, Manqi, Li, Haibin, Singh, Manjot, Li, Changwei, Liu, Kuo, Zhang, Feng, Yang, Xinghua, Luo, Yanxia, He, Yan, Wu, Lijuan, and Zheng, Deqiang
Abstract: Background: Few studies have focused on the prevalence of abdominal obesity in Chinese middle-aged and older adults with a normal body mass index (BMI). Furthermore, it is still unclear whether abdominal obesity is an independent risk factor for type 2 diabetes mellitus (T2DM). Participants with a normal BMI are usually neglected during assessments of abdominal obesity-associated T2DM risk since the current recommendations for medical interventions are mainly focused on overall body mass index rather than fat deposition patterns. Methods: In this study, 7942 normal-BMI participants aged over 45 years from the China Health and Retirement Longitudinal Study were included to assess the prevalence of abdominal obesity defined by waist circumference (WC) or waist-to-height ratio (WHtR). In addition, 4348 normal-BMI individuals with no diabetes at baseline were included to evaluate the association between abdominal obesity and the risk of T2DM with the Cox proportional hazards model. Results: The prevalence (95% confidence interval, CI) of increased WC and substantially increased WC among adults with a normal BMI was 22.0% (21.1%-22.9%) and 18.1% (17.3%-19.0%), respectively. The adjusted hazard ratios and 95% CIs for T2DM incidence were 1.39 (1.05– 1.85) and 1.89 (1.42– 2.53) for those with increased WC and substantially increased WC, respectively, compared to the individuals with a normal WC. Similar HRs were obtained for the association between WHtR and the risk of T2DM. In prediabetic patients, the HRs (95% CIs) for new-onset T2DM for those with increased WC and substantially increased WC were 1.85 (1.27– 2.69) and 2.46 (1.67– 3.61), respectively, when compared with individuals with normal WC. This positive association was observed in women but not in men or adults with normal glucose tolerance (NGT). Conclusion: Abdominal obesity is highly prevalent among middle-aged and older Chinese adults with a normal BMI, and maintaining a normal waist circumference may be benefi
Published: 2021

12. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Author: de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, Kavousi, Maryam, de Las Fuentes, Lisa, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, and Kavousi, Maryam
Abstract: Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Published: 2021

13. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Author: de las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F., Schwander, Karen, Bentley, Amy R., Brown, Michael R., Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I., Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P., Horimoto, A.R.V.R., Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K., Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Tayo, Bamidele O., Vojinovic, Dina, Warren, Helen R., Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B., Weiss, Stefan, Yanek, Lisa R., Amin, Najaf, Arking, Dan E., Arnett, Donna K., Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P., Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H. Janaka, de Vries, Paul S., Eiriksdottir, Gudny, Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Fox, Ervin F., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M. Arfan, Irvin, Marguerite R., Kähönen, Mika, Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Komulainen, Pirjo, Kraja, Aldi T., Krieger, J.E., Langefeld, Carl D., Li, Yize, Liang, Jingjing, Liewald, David C. M., Liu, Ching-Ti, Liu, Jianjun, Lohman, Kurt K., Mägi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mook-Kanamori, Dennis O., Nalls, Mike A., Nelson, Christopher P., Norris, Jill M., O’Connell, Jeff, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmer, Nicholette D., Pedersen, Nancy L., Perls, Thomas, Peters, Annette, Petersmann, Astrid, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Raffel, Leslie J., Rice, Treva K., Rotter, Jerome I., Rudan, Igor, Rueda-Ochoa, Oscar-Leonel, Sabanayagam, Charumathi, Salako, Babatunde L., Schreiner, Pamela J., Shikany, James M., Sidney, Stephen S., Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Tham, Yih Chung, Uitterlinden, André G., Vaidya, Dhananjay, van der Ende, M. Yldau, Waldenberger, Melanie, Wang, Lihua, Wang, Ya-Xing, Wei, Wen-Bin, Weir, David R., Wen, Wanqing, Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Bowden, Donald W., Deary, Ian J., Dörr, Marcus, Esko, Tõnu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kammerer, Candace M., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K. E., Marques-Vidal, Pedro, Penninx, Brenda W. J. H., Samani, Nilesh J., van der Harst, Pim, Wagenknecht, Lynne E., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Cooper, Richard S., Correa, Adolfo, Evans, Michele K., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Kritchevsky, Stephen B., Levy, Daniel, Palmas, Walter R., Pereira, A.C., Province, Michael M., Psaty, Bruce M., Ridker, Paul M., Rotimi, Charles N., Tai, E. Shyong, van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Rice, Kenneth, Gauderman, W. James, Morrison, Alanna C., North, Kari E., Kardia, Sharon L. R., Caulfield, Mark J., Elliott, Paul, Munroe, Patricia B., Franks, Paul W., Rao, Dabeeru C., Fornage, Myriam, de las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F., Schwander, Karen, Bentley, Amy R., Brown, Michael R., Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I., Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P., Horimoto, A.R.V.R., Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K., Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Tayo, Bamidele O., Vojinovic, Dina, Warren, Helen R., Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B., Weiss, Stefan, Yanek, Lisa R., Amin, Najaf, Arking, Dan E., Arnett, Donna K., Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P., Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H. Janaka, de Vries, Paul S., Eiriksdottir, Gudny, Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Fox, Ervin F., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M. Arfan, Irvin, Marguerite R., Kähönen, Mika, Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Komulainen, Pirjo, Kraja, Aldi T., Krieger, J.E., Langefeld, Carl D., Li, Yize, Liang, Jingjing, Liewald, David C. M., Liu, Ching-Ti, Liu, Jianjun, Lohman, Kurt K., Mägi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mook-Kanamori, Dennis O., Nalls, Mike A., Nelson, Christopher P., Norris, Jill M., O’Connell, Jeff, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmer, Nicholette D., Pedersen, Nancy L., Perls, Thomas, Peters, Annette, Petersmann, Astrid, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Raffel, Leslie J., Rice, Treva K., Rotter, Jerome I., Rudan, Igor, Rueda-Ochoa, Oscar-Leonel, Sabanayagam, Charumathi, Salako, Babatunde L., Schreiner, Pamela J., Shikany, James M., Sidney, Stephen S., Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Tham, Yih Chung, Uitterlinden, André G., Vaidya, Dhananjay, van der Ende, M. Yldau, Waldenberger, Melanie, Wang, Lihua, Wang, Ya-Xing, Wei, Wen-Bin, Weir, David R., Wen, Wanqing, Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Bowden, Donald W., Deary, Ian J., Dörr, Marcus, Esko, Tõnu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kammerer, Candace M., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K. E., Marques-Vidal, Pedro, Penninx, Brenda W. J. H., Samani, Nilesh J., van der Harst, Pim, Wagenknecht, Lynne E., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Cooper, Richard S., Correa, Adolfo, Evans, Michele K., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Kritchevsky, Stephen B., Levy, Daniel, Palmas, Walter R., Pereira, A.C., Province, Michael M., Psaty, Bruce M., Ridker, Paul M., Rotimi, Charles N., Tai, E. Shyong, van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Rice, Kenneth, Gauderman, W. James, Morrison, Alanna C., North, Kari E., Kardia, Sharon L. R., Caulfield, Mark J., Elliott, Paul, Munroe, Patricia B., Franks, Paul W., Rao, Dabeeru C., and Fornage, Myriam
Abstract: Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Published: 2021
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14. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Author: de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, A R V R, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Kilpeläinen, Tuomas O, de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, A R V R, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, and Kilpeläinen, Tuomas O
Abstract: Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Published: 2021

15. Prevalence of Abdominal Obesity in Chinese Middle-Aged and Older Adults with a Normal Body Mass Index and Its Association with Type 2 Diabetes Mellitus: A Nationally Representative Cohort Study from 2011 to 2018

Author: Chen, Xuan, Duan, Mingrui, Hou, Rui, Zheng, Manqi, Li, Haibin, Singh, Manjot, Li, Changwei, Liu, Kuo, Zhang, Feng, Yang, Xinghua, Luo, Yanxia, He, Yan, Wu, Lijuan, Zheng, Deqiang, Chen, Xuan, Duan, Mingrui, Hou, Rui, Zheng, Manqi, Li, Haibin, Singh, Manjot, Li, Changwei, Liu, Kuo, Zhang, Feng, Yang, Xinghua, Luo, Yanxia, He, Yan, Wu, Lijuan, and Zheng, Deqiang
Abstract: Background: Few studies have focused on the prevalence of abdominal obesity in Chinese middle-aged and older adults with a normal body mass index (BMI). Furthermore, it is still unclear whether abdominal obesity is an independent risk factor for type 2 diabetes mellitus (T2DM). Participants with a normal BMI are usually neglected during assessments of abdominal obesity-associated T2DM risk since the current recommendations for medical interventions are mainly focused on overall body mass index rather than fat deposition patterns. Methods: In this study, 7942 normal-BMI participants aged over 45 years from the China Health and Retirement Longitudinal Study were included to assess the prevalence of abdominal obesity defined by waist circumference (WC) or waist-to-height ratio (WHtR). In addition, 4348 normal-BMI individuals with no diabetes at baseline were included to evaluate the association between abdominal obesity and the risk of T2DM with the Cox proportional hazards model. Results: The prevalence (95% confidence interval, CI) of increased WC and substantially increased WC among adults with a normal BMI was 22.0% (21.1%-22.9%) and 18.1% (17.3%-19.0%), respectively. The adjusted hazard ratios and 95% CIs for T2DM incidence were 1.39 (1.05– 1.85) and 1.89 (1.42– 2.53) for those with increased WC and substantially increased WC, respectively, compared to the individuals with a normal WC. Similar HRs were obtained for the association between WHtR and the risk of T2DM. In prediabetic patients, the HRs (95% CIs) for new-onset T2DM for those with increased WC and substantially increased WC were 1.85 (1.27– 2.69) and 2.46 (1.67– 3.61), respectively, when compared with individuals with normal WC. This positive association was observed in women but not in men or adults with normal glucose tolerance (NGT). Conclusion: Abdominal obesity is highly prevalent among middle-aged and older Chinese adults with a normal BMI, and maintaining a normal waist circumference may be benefi
Published: 2021

16. Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus among Chinese: The Beijing longitudinal study of aging

Author: Cao, Xue, Tang, Zhe, Zhang, Jie, Li, Haibin, Singh, Manjot, Sun, Fei, Li, Xiaochun, Li, Changwei, Wang, Youxin, Guo, Xiuhua, Zheng, Deqiang, Cao, Xue, Tang, Zhe, Zhang, Jie, Li, Haibin, Singh, Manjot, Sun, Fei, Li, Xiaochun, Li, Changwei, Wang, Youxin, Guo, Xiuhua, and Zheng, Deqiang
Abstract: Background: Some previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration. Methods: In total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables. Results: Over the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62–1.55), 0.48 (95% CI: 0.27–0.85) and 0.44 (95% CI: 0.25–0.80) for individuals with HDL-C levels within the 1.15–1.39, 1.40–1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels < 1.15 mmol/L. Multiple sensitivity analyses similarly revealed reduced risk of diabetes incidence with increased HDL-C levels. Incorporating the levels of HDL-C into a multivariate model significantly enhanced the overall power of the predictive model (P values were 0.0296, 0.0011, respectively, for 5- and 10-year risk of diabetes). Conclusions: Levels of HDL-C were independently and negatively associated with the risk of the new-onset T2DM among
Published: 2021

17. Prevalence of Abdominal Obesity in Chinese Middle-Aged and Older Adults with a Normal Body Mass Index and Its Association with Type 2 Diabetes Mellitus: A Nationally Representative Cohort Study from 2011 to 2018

Author: Chen,Xuan, Duan,Mingrui, Hou,Rui, Zheng,Manqi, Li,Haibin, Singh,Manjot, Li,Changwei, Liu,Kuo, Zhang,Feng, Yang,Xinghua, Luo,Yanxia, He,Yan, Wu,Lijuan, Zheng,Deqiang, Chen,Xuan, Duan,Mingrui, Hou,Rui, Zheng,Manqi, Li,Haibin, Singh,Manjot, Li,Changwei, Liu,Kuo, Zhang,Feng, Yang,Xinghua, Luo,Yanxia, He,Yan, Wu,Lijuan, and Zheng,Deqiang
Abstract: Xuan Chen,1,&ast; Mingrui Duan,1,2,&ast; Rui Hou,1,2,&ast; Manqi Zheng,1,2 Haibin Li,3 Manjot Singh,4,5 Changwei Li,6 Kuo Liu,1,2 Feng Zhang,1,2 Xinghua Yang,1,2 Yanxia Luo,1,2 Yan He,1,2 Lijuan Wu,1,2 Deqiang Zheng1,2,7 1Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, Peopleâs Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, Peopleâs Republic of China; 3Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, Peopleâs Republic of China; 4Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, University of Western Australia, Crawley, WA, Australia; 5School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia; 6Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; 7Center for Primary Health Care Research, Lund University/Region SkÃ¥ne, MalmÃ¶, Sweden&ast;These authors contributed equally to this workCorrespondence: Deqiang ZhengDepartment of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, Peopleâs Republic of ChinaTel/Fax +86 10 8391 1497Email dqzheng@ccmu.edu.cnLijuan WuDepartment of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, Peopleâs Republic of ChinaTel +86 10 8391 1497Email xiaowu@ccmu.edu.cnBackground: Few studies have focused on the prevalence of abdominal obesity in Chinese middle-aged and older adults with a normal body mass index (BMI). Furthermore, it is still unclear whether abdominal obesity is an independent risk factor for type 2 diabetes mellitus (T2DM). Participants with a normal BMI are usua
Published: 2021

18. Associations between social and intellectual activities with cognitive trajectories in Chinese middle-aged and older adults: A nationally representative cohort study

Author: Li, Haibin, Li, Changwei, Wang, Anxin, Qi, Yanling, Feng, Wei, Hou, Chengbei, Tao, Lixin, Liu, Xiangtong, Li, Xia, Wang, Wei, Zheng, Deqiang, Guo, Xiuhua, Li, Haibin, Li, Changwei, Wang, Anxin, Qi, Yanling, Feng, Wei, Hou, Chengbei, Tao, Lixin, Liu, Xiangtong, Li, Xia, Wang, Wei, Zheng, Deqiang, and Guo, Xiuhua
Abstract: BACKGROUND: Associations between the frequency of social and intellectual activities and cognitive trajectories are understudied in Chinese middle-aged and older adults. We aimed to examine this association in a nationally representative longitudinal study. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative sample of Chinese middle-aged and older participants. The frequency of social and intellectual activities was measured at baseline. Interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial skills and the calculation of combined global scores were assessed every 2 years from 2011 to 2016. Cognitive aging trajectories over time were analyzed using group-based trajectory modeling, and the associations of the trajectory memberships with social and intellectual activities were analyzed using multinomial logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were reported. RESULTS: Among 8204 participants aged 50-75 years at baseline, trajectory analysis identified three longitudinal patterns of cognitive function based on the global cognitive scores: "persistently low trajectory" (n = 1550, 18.9%), "persistently moderate trajectory" (n = 3194, 38.9%), and "persistently high trajectory" (n = 3460, 42.2%). After adjustment for sociodemographic variables, lifestyles, geriatric symptoms, and health conditions, more frequent intellectual activities (OR 0.54, 95% CI 0.38-0.77) and social activities (OR 0.79, 95% CI 0.65-0.95) were both associated with a lower likelihood of being in the "persistently low trajectory" for global cognitive function. CONCLUSIONS: These findings suggested that more frequent social and intellectual activities were associated with more favorable cognitive aging trajectories.
Published: 2020

19. Associations between social and intellectual activities with cognitive trajectories in Chinese middle-aged and older adults: A nationally representative cohort study

Author: Li, Haibin, Li, Changwei, Wang, Anxin, Qi, Yanling, Feng, Wei, Hou, Chengbei, Tao, Lixin, Liu, Xiangtong, Li, Xia, Wang, Wei, Zheng, Deqiang, Guo, Xiuhua, Li, Haibin, Li, Changwei, Wang, Anxin, Qi, Yanling, Feng, Wei, Hou, Chengbei, Tao, Lixin, Liu, Xiangtong, Li, Xia, Wang, Wei, Zheng, Deqiang, and Guo, Xiuhua
Abstract: BACKGROUND: Associations between the frequency of social and intellectual activities and cognitive trajectories are understudied in Chinese middle-aged and older adults. We aimed to examine this association in a nationally representative longitudinal study. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative sample of Chinese middle-aged and older participants. The frequency of social and intellectual activities was measured at baseline. Interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial skills and the calculation of combined global scores were assessed every 2 years from 2011 to 2016. Cognitive aging trajectories over time were analyzed using group-based trajectory modeling, and the associations of the trajectory memberships with social and intellectual activities were analyzed using multinomial logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were reported. RESULTS: Among 8204 participants aged 50-75 years at baseline, trajectory analysis identified three longitudinal patterns of cognitive function based on the global cognitive scores: "persistently low trajectory" (n = 1550, 18.9%), "persistently moderate trajectory" (n = 3194, 38.9%), and "persistently high trajectory" (n = 3460, 42.2%). After adjustment for sociodemographic variables, lifestyles, geriatric symptoms, and health conditions, more frequent intellectual activities (OR 0.54, 95% CI 0.38-0.77) and social activities (OR 0.79, 95% CI 0.65-0.95) were both associated with a lower likelihood of being in the "persistently low trajectory" for global cognitive function. CONCLUSIONS: These findings suggested that more frequent social and intellectual activities were associated with more favorable cognitive aging trajectories.
Published: 2020

20. Long-Term Trends in Hospitalization and Outcomes in Adult Patients with Exacerbation of Chronic Obstructive Pulmonary Disease in Beijing, China, from 2008 to 2017

Author: Liang,Lirong, Li,Changwei, Shen,Ye, Rong,Hengmo, Jing,Hang, Tong,Zhaohui, Liang,Lirong, Li,Changwei, Shen,Ye, Rong,Hengmo, Jing,Hang, and Tong,Zhaohui
Abstract: Lirong Liang,1 Changwei Li,2 Ye Shen,2 Hengmo Rong,3 Hang Jing,1 Zhaohui Tong3 1Department of Clinical Epidemiology and Tobacco Dependence Treatment Research, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, Athens, GA, USA; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zhaohui TongDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, People’s Republic of ChinaTel +86-10-85231610Fax +86-10-65060167Email tongzhaohuicy@sina.comBackground and Objective: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. We aimed to evaluate the temporal trends in hospitalization and mortality from acute exacerbation of COPD (AECOPD) and the associated financial costs over a 10-year period in Beijing, China.Methods: Hospital admission records from 2008 to 2017 for all patients aged ≥ 20 years with a primary discharge diagnosis of AECOPD were retrieved from the Beijing Public Health Information Center Database. Joinpoint regression was used to analyze trends and calculate the annual percentage change (APC) and average annual percent change (AAPC) for AECOPD hospitalization and mortality.Results: A total of 337,802 AECOPD cases were recorded from 2008 to 2017. An inverse U-shaped trend in the AECOPD hospitalization rate was observed, showing an increase from 150.2 per 100,000 inhabitants in 2008 to 218.7 per 100,000 inhabitants in 2014 (APC: 5.5%, 95% CI: 2.9– 8.2), before declining to 161.13 per 10
Published: 2020

21. Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.

Author: Li, Changwei, Li, Changwei, Kim, Yun Kyoung, Dorajoo, Rajkumar, Li, Huaixing, Lee, I-Te, Cheng, Ching-Yu, He, Meian, Sheu, Wayne H-H, Guo, Xiuqing, Ganesh, Santhi K, He, Jiang, Lee, Juyoung, Liu, Jianjun, Hu, Yao, Rao, Dabeeru C, Tsai, Fuu-Jen, Koh, Jia Yu, Hu, Hua, Liang, Kae-Woei, Palmas, Walter, Hixson, James E, Han, Sohee, Teo, Yik-Ying, Wang, Yiqin, Chen, Jing, Lu, Chieh Hsiang, Zheng, Yingfeng, Gui, Lixuan, Lee, Wen-Jane, Yao, Jie, Gu, Dongfeng, Han, Bok-Ghee, Sim, Xueling, Sun, Liang, Zhao, Jinying, Chen, Chien-Hsiun, Kumari, Neelam, He, Yunfeng, Taylor, Kent D, Raffel, Leslie J, Moon, Sanghoon, Rotter, Jerome I, Ida Chen, Yii-der, Wu, Tangchun, Wong, Tien Yin, Wu, Jer-Yuarn, Lin, Xu, Tai, E-Shyong, Kim, Bong-Jo, Kelly, Tanika N, Li, Changwei, Li, Changwei, Kim, Yun Kyoung, Dorajoo, Rajkumar, Li, Huaixing, Lee, I-Te, Cheng, Ching-Yu, He, Meian, Sheu, Wayne H-H, Guo, Xiuqing, Ganesh, Santhi K, He, Jiang, Lee, Juyoung, Liu, Jianjun, Hu, Yao, Rao, Dabeeru C, Tsai, Fuu-Jen, Koh, Jia Yu, Hu, Hua, Liang, Kae-Woei, Palmas, Walter, Hixson, James E, Han, Sohee, Teo, Yik-Ying, Wang, Yiqin, Chen, Jing, Lu, Chieh Hsiang, Zheng, Yingfeng, Gui, Lixuan, Lee, Wen-Jane, Yao, Jie, Gu, Dongfeng, Han, Bok-Ghee, Sim, Xueling, Sun, Liang, Zhao, Jinying, Chen, Chien-Hsiun, Kumari, Neelam, He, Yunfeng, Taylor, Kent D, Raffel, Leslie J, Moon, Sanghoon, Rotter, Jerome I, Ida Chen, Yii-der, Wu, Tangchun, Wong, Tien Yin, Wu, Jer-Yuarn, Lin, Xu, Tai, E-Shyong, Kim, Bong-Jo, and Kelly, Tanika N
Abstract: BackgroundGenome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP.Methods and resultsWe conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P<5.0×10-8 and 2.5×10-6, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P=5.03×10-8, stage-2 P=8.64×10-3, joint P=2.63×10-8) and mean arterial pressure (stage-1 P=3.59×10-9, stage-2 P=2.35×10-2, joint P=2.64×10-8). Three previously reported BP loci (WBP1L, NT5C2, and ATP2B1) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P=8.55×10-6, stage-2 P=1.62×10-5, joint P=3.28×10-9) and mean arterial pressure (stage-1 P=9.19×10-7, stage-2 P=9.69×10-5, joint P=2.15×10-9) phenotypes. Fourteen genes (TMEM180, ACTR1A, SUFU, ARL3, SFXN2, WBP1L, CYP17A1, C10orf32, C10orf32-ASMT, AS3MT, CNNM2, and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (P=1.27×10-4 and 3.30×10-4, respectively).ConclusionsWe identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians.
Published: 2017

22. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., Loos, Ruth J. F., Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., and Loos, Ruth J. F.
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019
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23. A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Author: Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., Morrison, Alanna C., Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., and Morrison, Alanna C.
Abstract: Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
Published: 2019
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24. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author: de Vries, Paul S., Brown, Michael R., Bentley, Amy R., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T., Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Laguzzi, Federica, Lee, Joseph H., Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Riaz, Muhammad, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., 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, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renee, de Silva, H. Janaka, Ding, Jingzhong, Dominiczak, Anna F., Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Grabe, Hans J., Grove, Megan L., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Howard, Barbara V., Ikram, M. Arfan, Jacobs, David R., Jr., Johnson, Craig, Jonas, Jost Bruno, Kammerer, Candace M., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Koistinen, Heikki A., Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Steve B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lemaitre, Rozenn N., Li, Yize, Liang, Jingjing, Liu, Jianjun, Liu, Kiang, Loh, Marie, Louie, Tin, Magi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Mosley, Thomas H., Jr., Mukamal, Kenneth J., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Sotoodehnia, Nona, O'Connell, Jeff R., Palmer, Nicholette D., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Reiner, Alex P., Rice, Treva K., Rich, Stephen S., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tan, Nicholas, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., van Heemst, Diana, Vuckovic, Dragana, Waldenberger, Melanie, Wang, Lihua, Wang, Yujie, Wang, Zhe, Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Leander, Karin, Lehtimaki, Terho, Magnusson, Patrik K. E., Penninx, Brenda, Pereira, Alexandre C., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Zheng, Wei, Elliott, Paul, North, Kari E., Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Liu, Ching-Ti, Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Kardia, Sharon L. R., Zhu, Xiaofeng, Rotimi, Charles N., Mook-Kanamori, Dennis O., Fornage, Myriam, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Liu, Jingmin, Rotter, Jerome I., Gauderman, W. James, Province, Michael A., Munroe, Patricia B., Rice, Kenneth, Chasman, Daniel I., Cupples, L. Adrienne, Rao, Dabeeru C., Morrison, Alanna C., de Vries, Paul S., Brown, Michael R., Bentley, Amy R., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T., Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Laguzzi, Federica, Lee, Joseph H., Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Riaz, Muhammad, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., 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, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renee, de Silva, H. Janaka, Ding, Jingzhong, Dominiczak, Anna F., Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Grabe, Hans J., Grove, Megan L., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Howard, Barbara V., Ikram, M. Arfan, Jacobs, David R., Jr., Johnson, Craig, Jonas, Jost Bruno, Kammerer, Candace M., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Koistinen, Heikki A., Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Steve B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lemaitre, Rozenn N., Li, Yize, Liang, Jingjing, Liu, Jianjun, Liu, Kiang, Loh, Marie, Louie, Tin, Magi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Mosley, Thomas H., Jr., Mukamal, Kenneth J., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Sotoodehnia, Nona, O'Connell, Jeff R., Palmer, Nicholette D., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Reiner, Alex P., Rice, Treva K., Rich, Stephen S., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tan, Nicholas, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., van Heemst, Diana, Vuckovic, Dragana, Waldenberger, Melanie, Wang, Lihua, Wang, Yujie, Wang, Zhe, Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Leander, Karin, Lehtimaki, Terho, Magnusson, Patrik K. E., Penninx, Brenda, Pereira, Alexandre C., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Zheng, Wei, Elliott, Paul, North, Kari E., Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Liu, Ching-Ti, Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Kardia, Sharon L. R., Zhu, Xiaofeng, Rotimi, Charles N., Mook-Kanamori, Dennis O., Fornage, Myriam, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Liu, Jingmin, Rotter, Jerome I., Gauderman, W. James, Province, Michael A., Munroe, Patricia B., Rice, Kenneth, Chasman, Daniel I., Cupples, L. Adrienne, Rao, Dabeeru C., and Morrison, Alanna C.
Abstract: 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.
Published: 2019
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25. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., Loos, Ruth J. F., Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., and Loos, Ruth J. F.
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019
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26. Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Author: Bentley, Amy R., Sung, Yun J., Brown, Michael R., Winkler, Thomas W., Kraja, Aldi T., Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel, I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M., Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert, V, Tajuddin, Salman M., Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Hung, Yi-Jen, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Prins, Bram, Riaz, Muhammad, Robino, Antonietta, Said, M. Abdullah, Schupf, Nicole, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Wang, Tzung-Dau, Wang, Yajuan, Ware, Erin B., Wen, Wanqing, Xiang, Yong-Bing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Adeyemo, Adebowale, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Arzumanyan, Zorayr, Aung, Tin, Ballantyne, Christie, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Broeckel, Ulrich, Brown, Morris, Cade, Brian E., Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Christensen, Kaare, Concas, Maria Pina, Connell, John M., de las Fuentes, Lisa, de Silva, H. Janaka, de Vries, Paul S., Doumatey, Ayo, Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Floyd, James S., Forouhi, Nita G., Forrester, Terrence, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gharib, Sina A., Gigante, Bruna, Giulianini, Franco, Grabe, Hans J., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Ikram, M. Arfan, Jia, Yucheng, Joehanes, Roby, Johnson, Craig, Jonas, Jost Bruno, Justice, Anne E., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Liang, Jingjing, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Kiang, Loh, Marie, Lohman, Kurt K., Louie, Tin, Luzzi, Anna, Magi, Reedik, Mahajan, Anubha, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Morris, Andrew P., Murray, Alison D., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., North, Kari E., O'Connell, Jeffrey R., Palmer, Nicholette D., Papanicolau, George J., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raitakari, Olli T., Reiner, Alex P., Renstrom, Frida, Rice, Treva K., Rich, Stephen S., Robinson, Jennifer G., Rose, Lynda M., Rosendaal, Frits R., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Tiemeier, Henning, Turner, Stephen T., Uitterlinden, Andre G., van Heemst, Diana, Waldenberger, Melanie, Wang, Heming, Wang, Lan, Wang, Lihua, Wei, Wen Bin, Williams, Christine A., Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Young, Kristin, Yu, Caizheng, Yuan, Jian-Min, Zhou, Jie, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Cooper, Richard S., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kammerer, Candace M., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Laurie, Cathy C., Lee, I-Te, Lehtimaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Pereira, Alexandre C., Rauramaa, Rainer, Redline, Susan, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Jun-Sing, Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zeggini, Eleftheria, Zheng, Wei, Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Mook-Kanamori, Dennis O., Fornage, Myriam, Province, Michael A., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Franceschini, Nora, Rotter, Jerome, I, Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Rao, Dabeeru C., Rotimi, Charles N., Cupples, L. Adrienne, Bentley, Amy R., Sung, Yun J., Brown, Michael R., Winkler, Thomas W., Kraja, Aldi T., Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel, I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M., Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert, V, Tajuddin, Salman M., Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Hung, Yi-Jen, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Prins, Bram, Riaz, Muhammad, Robino, Antonietta, Said, M. Abdullah, Schupf, Nicole, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Wang, Tzung-Dau, Wang, Yajuan, Ware, Erin B., Wen, Wanqing, Xiang, Yong-Bing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Adeyemo, Adebowale, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Arzumanyan, Zorayr, Aung, Tin, Ballantyne, Christie, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Broeckel, Ulrich, Brown, Morris, Cade, Brian E., Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Christensen, Kaare, Concas, Maria Pina, Connell, John M., de las Fuentes, Lisa, de Silva, H. Janaka, de Vries, Paul S., Doumatey, Ayo, Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Floyd, James S., Forouhi, Nita G., Forrester, Terrence, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gharib, Sina A., Gigante, Bruna, Giulianini, Franco, Grabe, Hans J., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Ikram, M. Arfan, Jia, Yucheng, Joehanes, Roby, Johnson, Craig, Jonas, Jost Bruno, Justice, Anne E., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Liang, Jingjing, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Kiang, Loh, Marie, Lohman, Kurt K., Louie, Tin, Luzzi, Anna, Magi, Reedik, Mahajan, Anubha, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Morris, Andrew P., Murray, Alison D., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., North, Kari E., O'Connell, Jeffrey R., Palmer, Nicholette D., Papanicolau, George J., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raitakari, Olli T., Reiner, Alex P., Renstrom, Frida, Rice, Treva K., Rich, Stephen S., Robinson, Jennifer G., Rose, Lynda M., Rosendaal, Frits R., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Tiemeier, Henning, Turner, Stephen T., Uitterlinden, Andre G., van Heemst, Diana, Waldenberger, Melanie, Wang, Heming, Wang, Lan, Wang, Lihua, Wei, Wen Bin, Williams, Christine A., Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Young, Kristin, Yu, Caizheng, Yuan, Jian-Min, Zhou, Jie, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Cooper, Richard S., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kammerer, Candace M., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Laurie, Cathy C., Lee, I-Te, Lehtimaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Pereira, Alexandre C., Rauramaa, Rainer, Redline, Susan, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Jun-Sing, Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zeggini, Eleftheria, Zheng, Wei, Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Mook-Kanamori, Dennis O., Fornage, Myriam, Province, Michael A., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Franceschini, Nora, Rotter, Jerome, I, Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Rao, Dabeeru C., Rotimi, Charles N., and Cupples, L. Adrienne
Abstract: The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.
Published: 2019
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27. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., Loos, Ruth J. F., Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., and Loos, Ruth J. F.
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019
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28. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Author: Noordam, Raymond, Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O, de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick CN, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, Uitterlinden, André G, Noordam, Raymond, Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O, de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick CN, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, and Uitterlinden, André G
Abstract: Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
Published: 2019

29. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Author: Kilpeläinen, Tuomas O, Kilpeläinen, Tuomas O, Bentley, Amy R, Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W, Jakupović, Hermina, Chasman, Daniel I, Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R, de Las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F, Kho, Minjung, Musani, Solomon K, Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Li, Changwei, Lohman, Kurt K, Marten, Jonathan, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Zhao, Jing Hua, Kraja, Aldi T, Kühnel, Brigitte, Laguzzi, Federica, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M, Takeuchi, Fumihiko, van der Most, Peter J, Varga, Tibor V, Verweij, Niek, Ware, Erin B, Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R, Amin, Najaf, Arnett, Donna K, Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickaël, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renée, de Silva, H Janaka, de Vries, Paul S, Demirkan, Ayşe, Ding, Jingzhong, Eaton, Charles B, Faul, Jessica D, Friedlander, Yechiel, Gabriel, Kelley P, Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C, Ikram, M Arfan, Jonas, Jost B, Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E, Kilpeläinen, Tuomas O, Kilpeläinen, Tuomas O, Bentley, Amy R, Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W, Jakupović, Hermina, Chasman, Daniel I, Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R, de Las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F, Kho, Minjung, Musani, Solomon K, Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Li, Changwei, Lohman, Kurt K, Marten, Jonathan, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Zhao, Jing Hua, Kraja, Aldi T, Kühnel, Brigitte, Laguzzi, Federica, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M, Takeuchi, Fumihiko, van der Most, Peter J, Varga, Tibor V, Verweij, Niek, Ware, Erin B, Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R, Amin, Najaf, Arnett, Donna K, Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickaël, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renée, de Silva, H Janaka, de Vries, Paul S, Demirkan, Ayşe, Ding, Jingzhong, Eaton, Charles B, Faul, Jessica D, Friedlander, Yechiel, Gabriel, Kelley P, Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C, Ikram, M Arfan, Jonas, Jost B, Koh, Woon-Puay, Komulainen, Pirjo, and Krieger, Jose E
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019

30. Novel serum metabolites associate with cognition phenotypes among Bogalusa Heart Study participants.

Author: Shi, Mengyao, Shi, Mengyao, Bazzano, Lydia A, He, Jiang, Gu, Xiaoying, Li, Changwei, Li, Shengxu, Yaffe, Kristine, Kinchen, Jason M, Stuchlik, Patrick, Mi, Xuenan, Nierenberg, Jovia L, Razavi, Alexander C, Kelly, Tanika N, Shi, Mengyao, Shi, Mengyao, Bazzano, Lydia A, He, Jiang, Gu, Xiaoying, Li, Changwei, Li, Shengxu, Yaffe, Kristine, Kinchen, Jason M, Stuchlik, Patrick, Mi, Xuenan, Nierenberg, Jovia L, Razavi, Alexander C, and Kelly, Tanika N
Abstract: BackgroundMetabolomics study provides an opportunity to identify novel molecular determinants of altered cognitive function.MethodsDuring 2013 to 2016 Bogalusa Heart Study (BHS) visit, 1,177 participants underwent untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy metabolomics profiling. Global cognition and five cognition domains were also assessed. The cross-sectional associations of single metabolites with cognition were tested using multiple linear regression models. Weighted correlation network analysis was used to examine the covariable-adjusted correlations of modules of co-abundant metabolites with cognition. Analyses were conducted in the overall sample and according to both ethnicity and sex.ResultsFive known metabolites and two metabolite modules robustly associated with cognition across overall and stratified analyses. Two metabolites were from lipid sub-pathways including fatty acid metabolism [9-hydroxystearate; minimum P-value (min-P)=1.11×10-5], and primary bile acid metabolism (glyco-alpha-muricholate; min-P=4.10×10-5). One metabolite from the glycogen metabolism sub-pathway (maltose; min-P=9.77×10-6), one from the polyamine metabolism sub-pathway (N-acetyl-isoputreanine; min-P=1.03×10-5), and one from the purine metabolism sub-pathway (7-methylguanine; min-P=1.19×10-5) were also identified. Two metabolite modules reflecting bile acid metabolism and androgenic steroids correlated with cognition (min-P=5.00×10-4 and 3.00×10-3, respectively).ConclusionThe novel associations of 5 known metabolites and 2 metabolite modules with cognition provide insights into the physiological mechanisms regulating cognitive function.
Published: 2019

31. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Author: Kilpeläinen, Tuomas O, Kilpeläinen, Tuomas O, Bentley, Amy R, Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W, Jakupović, Hermina, Chasman, Daniel I, Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R, de Las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F, Kho, Minjung, Musani, Solomon K, Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Li, Changwei, Lohman, Kurt K, Marten, Jonathan, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Zhao, Jing Hua, Kraja, Aldi T, Kühnel, Brigitte, Laguzzi, Federica, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M, Takeuchi, Fumihiko, van der Most, Peter J, Varga, Tibor V, Verweij, Niek, Ware, Erin B, Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R, Amin, Najaf, Arnett, Donna K, Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickaël, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renée, de Silva, H Janaka, de Vries, Paul S, Demirkan, Ayşe, Ding, Jingzhong, Eaton, Charles B, Faul, Jessica D, Friedlander, Yechiel, Gabriel, Kelley P, Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C, Ikram, M Arfan, Jonas, Jost B, Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E, Kilpeläinen, Tuomas O, Kilpeläinen, Tuomas O, Bentley, Amy R, Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W, Jakupović, Hermina, Chasman, Daniel I, Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R, de Las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F, Kho, Minjung, Musani, Solomon K, Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Li, Changwei, Lohman, Kurt K, Marten, Jonathan, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Zhao, Jing Hua, Kraja, Aldi T, Kühnel, Brigitte, Laguzzi, Federica, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M, Takeuchi, Fumihiko, van der Most, Peter J, Varga, Tibor V, Verweij, Niek, Ware, Erin B, Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R, Amin, Najaf, Arnett, Donna K, Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickaël, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renée, de Silva, H Janaka, de Vries, Paul S, Demirkan, Ayşe, Ding, Jingzhong, Eaton, Charles B, Faul, Jessica D, Friedlander, Yechiel, Gabriel, Kelley P, Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C, Ikram, M Arfan, Jonas, Jost B, Koh, Woon-Puay, Komulainen, Pirjo, and Krieger, Jose E
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019

32. Novel serum metabolites associate with cognition phenotypes among Bogalusa Heart Study participants.

Author: Shi, Mengyao, Shi, Mengyao, Bazzano, Lydia A, He, Jiang, Gu, Xiaoying, Li, Changwei, Li, Shengxu, Yaffe, Kristine, Kinchen, Jason M, Stuchlik, Patrick, Mi, Xuenan, Nierenberg, Jovia L, Razavi, Alexander C, Kelly, Tanika N, Shi, Mengyao, Shi, Mengyao, Bazzano, Lydia A, He, Jiang, Gu, Xiaoying, Li, Changwei, Li, Shengxu, Yaffe, Kristine, Kinchen, Jason M, Stuchlik, Patrick, Mi, Xuenan, Nierenberg, Jovia L, Razavi, Alexander C, and Kelly, Tanika N
Abstract: BackgroundMetabolomics study provides an opportunity to identify novel molecular determinants of altered cognitive function.MethodsDuring 2013 to 2016 Bogalusa Heart Study (BHS) visit, 1,177 participants underwent untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy metabolomics profiling. Global cognition and five cognition domains were also assessed. The cross-sectional associations of single metabolites with cognition were tested using multiple linear regression models. Weighted correlation network analysis was used to examine the covariable-adjusted correlations of modules of co-abundant metabolites with cognition. Analyses were conducted in the overall sample and according to both ethnicity and sex.ResultsFive known metabolites and two metabolite modules robustly associated with cognition across overall and stratified analyses. Two metabolites were from lipid sub-pathways including fatty acid metabolism [9-hydroxystearate; minimum P-value (min-P)=1.11×10-5], and primary bile acid metabolism (glyco-alpha-muricholate; min-P=4.10×10-5). One metabolite from the glycogen metabolism sub-pathway (maltose; min-P=9.77×10-6), one from the polyamine metabolism sub-pathway (N-acetyl-isoputreanine; min-P=1.03×10-5), and one from the purine metabolism sub-pathway (7-methylguanine; min-P=1.19×10-5) were also identified. Two metabolite modules reflecting bile acid metabolism and androgenic steroids correlated with cognition (min-P=5.00×10-4 and 3.00×10-3, respectively).ConclusionThe novel associations of 5 known metabolites and 2 metabolite modules with cognition provide insights into the physiological mechanisms regulating cognitive function.
Published: 2019

33. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Author: Noordam, Raymond, Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O, de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick CN, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, Uitterlinden, André G, Noordam, Raymond, Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O, de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick CN, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, and Uitterlinden, André G
Abstract: Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
Published: 2019

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

Author: de Vries, Paul S, de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, 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, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, de Vries, Paul S, de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, 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, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, and Giulianini, Franco
Abstract: 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 × 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 × 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.
Published: 2019

35. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., Loos, Ruth J. F., Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., and Loos, Ruth J. F.
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019
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36. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author: de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea R V R, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Zhao, Jing Hua, Kilpeläinen, Tuomas O, V Varga, Tibor, de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea R V R, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Zhao, Jing Hua, Kilpeläinen, Tuomas O, and V Varga, Tibor
Abstract: An individual'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 multi-ancestry 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 five ancestry groups. Genetic main and interaction effects were jointly assessed by 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 × 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 Stage 1 and Stage 2, 147 independent loci were associated with lipid levels at P < 5 × 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 (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.
Published: 2019

37. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpeläinen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupović, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R.V.R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Zhao, Jing Hua, Loos, Ruth J.F., V Varga, Tibor, Kilpeläinen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupović, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R.V.R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Zhao, Jing Hua, Loos, Ruth J.F., and V Varga, Tibor
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019

38. A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Author: Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renstrom, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., Morrison, Alanna C., Oskari Kilpeläinen, Tuomas, Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renstrom, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., Morrison, Alanna C., and Oskari Kilpeläinen, Tuomas
Published: 2019

39. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Author: Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O., de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick C N, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, Uitterlinden, André G, van Duijn, Cornelia M, Völzke, Henry, Waldenberger, Melanie, Wallance, Robert B, van Dijk, Ko Willems, Yu, Caizheng, Zonderman, Alan B, Becker, Diane M, Elliott, Paul, Esko, Tõnu, Gieger, Christian, Grabe, Hans J, Lakka, Timo A, Lehtimäki, Terho, North, Kari E, Penninx, Brenda W J H, Vollenweider, Peter, Wagenknecht, Lynne E, Wu, Tangchun, Xiang, Yong-Bing, Zheng, Wei, Arnett, Donna K, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Kardia, Sharon, Kelly, Tanika N, Kritchevsky, Stephen B, Loos, Ruth J F, Pereira, Alexandre C, Province, Mike, Psaty, Bruce M, Rotimi, Charles, Zhu, Xiaofeng, Amin, Najaf, Cupples, L Adrienne, Fornage, Myriam, Fox, Ervin F, Guo, Xiuqing, Gauderman, W James, Rice, Kenneth, Kooperberg, Charles, Munroe, Patricia B, Liu, Ching-Ti, Morrison, Alanna C, Rao, Dabeeru C, van Heemst, Diana, Redline, Susan, Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O., de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick C N, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, Uitterlinden, André G, van Duijn, Cornelia M, Völzke, Henry, Waldenberger, Melanie, Wallance, Robert B, van Dijk, Ko Willems, Yu, Caizheng, Zonderman, Alan B, Becker, Diane M, Elliott, Paul, Esko, Tõnu, Gieger, Christian, Grabe, Hans J, Lakka, Timo A, Lehtimäki, Terho, North, Kari E, Penninx, Brenda W J H, Vollenweider, Peter, Wagenknecht, Lynne E, Wu, Tangchun, Xiang, Yong-Bing, Zheng, Wei, Arnett, Donna K, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Kardia, Sharon, Kelly, Tanika N, Kritchevsky, Stephen B, Loos, Ruth J F, Pereira, Alexandre C, Province, Mike, Psaty, Bruce M, Rotimi, Charles, Zhu, Xiaofeng, Amin, Najaf, Cupples, L Adrienne, Fornage, Myriam, Fox, Ervin F, Guo, Xiuqing, Gauderman, W James, Rice, Kenneth, Kooperberg, Charles, Munroe, Patricia B, Liu, Ching-Ti, Morrison, Alanna C, Rao, Dabeeru C, van Heemst, Diana, and Redline, Susan
Abstract: Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
Published: 2019

40. Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Author: Bentley, Amy R, Sung, Yun J, Brown, Michael R, Winkler, Thomas W, Kraja, Aldi T, Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M, Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, Zhao, Jing Hua, Christensen, Kaare, Kilpeläinen, Tuomas O, Wang, Jun-Sing, Loos, Ruth J F, V Varga, Tibor, Bentley, Amy R, Sung, Yun J, Brown, Michael R, Winkler, Thomas W, Kraja, Aldi T, Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M, Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, Zhao, Jing Hua, Christensen, Kaare, Kilpeläinen, Tuomas O, Wang, Jun-Sing, Loos, Ruth J F, and V Varga, Tibor
Abstract: The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.
Published: 2019

41. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Author: Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O., de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick C N, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, Uitterlinden, André G, van Duijn, Cornelia M, Völzke, Henry, Waldenberger, Melanie, Wallance, Robert B, van Dijk, Ko Willems, Yu, Caizheng, Zonderman, Alan B, Becker, Diane M, Elliott, Paul, Esko, Tõnu, Gieger, Christian, Grabe, Hans J, Lakka, Timo A, Lehtimäki, Terho, North, Kari E, Penninx, Brenda W J H, Vollenweider, Peter, Wagenknecht, Lynne E, Wu, Tangchun, Xiang, Yong-Bing, Zheng, Wei, Arnett, Donna K, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Kardia, Sharon, Kelly, Tanika N, Kritchevsky, Stephen B, Loos, Ruth J F, Pereira, Alexandre C, Province, Mike, Psaty, Bruce M, Rotimi, Charles, Zhu, Xiaofeng, Amin, Najaf, Cupples, L Adrienne, Fornage, Myriam, Fox, Ervin F, Guo, Xiuqing, Gauderman, W James, Rice, Kenneth, Kooperberg, Charles, Munroe, Patricia B, Liu, Ching-Ti, Morrison, Alanna C, Rao, Dabeeru C, van Heemst, Diana, Redline, Susan, Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O., de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick C N, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, Uitterlinden, André G, van Duijn, Cornelia M, Völzke, Henry, Waldenberger, Melanie, Wallance, Robert B, van Dijk, Ko Willems, Yu, Caizheng, Zonderman, Alan B, Becker, Diane M, Elliott, Paul, Esko, Tõnu, Gieger, Christian, Grabe, Hans J, Lakka, Timo A, Lehtimäki, Terho, North, Kari E, Penninx, Brenda W J H, Vollenweider, Peter, Wagenknecht, Lynne E, Wu, Tangchun, Xiang, Yong-Bing, Zheng, Wei, Arnett, Donna K, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Kardia, Sharon, Kelly, Tanika N, Kritchevsky, Stephen B, Loos, Ruth J F, Pereira, Alexandre C, Province, Mike, Psaty, Bruce M, Rotimi, Charles, Zhu, Xiaofeng, Amin, Najaf, Cupples, L Adrienne, Fornage, Myriam, Fox, Ervin F, Guo, Xiuqing, Gauderman, W James, Rice, Kenneth, Kooperberg, Charles, Munroe, Patricia B, Liu, Ching-Ti, Morrison, Alanna C, Rao, Dabeeru C, van Heemst, Diana, and Redline, Susan
Abstract: Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
Published: 2019

42. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpeläinen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupović, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R.V.R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Zhao, Jing Hua, Loos, Ruth J.F., V Varga, Tibor, Kilpeläinen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupović, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R.V.R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Zhao, Jing Hua, Loos, Ruth J.F., and V Varga, Tibor
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019

43. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., Loos, Ruth J. F., Kilpelainen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupovic, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kuehnel, Brigitte, Laguzzi, Federica, Lyytikainen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickael, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renee, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayse, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltan, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Magi, Reedik, Manichaikul, Ani, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Jr., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O'Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, Andre G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimaaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. James, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., and Loos, Ruth J. F.
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Published: 2019
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44. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author: Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuhnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L., Canouil, Mickael, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, Fuentes, Lisa de las, de Mutsert, Renee, de Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelos, Fau, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charles, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Magi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, NelsonNona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thomas, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, Andre G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Bin Wei, Wen, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltan, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimaki, Terho, Study, Lifelines Cohort, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Poiasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Gauderman, W. James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., Levy, Daniel, Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuhnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L., Canouil, Mickael, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, Fuentes, Lisa de las, de Mutsert, Renee, de Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelos, Fau, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charles, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Magi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, NelsonNona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thomas, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, Andre G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Bin Wei, Wen, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltan, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimaki, Terho, Study, Lifelines Cohort, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Poiasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Gauderman, W. James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., and Levy, Daniel
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
Published: 2018
Full Text: View/download PDF

45. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author: Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuhnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L., Canouil, Mickael, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, Fuentes, Lisa de las, de Mutsert, Renee, de Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelos, Fau, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charles, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Magi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, NelsonNona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thomas, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, Andre G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Bin Wei, Wen, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltan, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimaki, Terho, Study, Lifelines Cohort, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Poiasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Gauderman, W. James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., Levy, Daniel, Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuhnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L., Canouil, Mickael, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, Fuentes, Lisa de las, de Mutsert, Renee, de Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelos, Fau, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charles, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Magi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, NelsonNona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thomas, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, Andre G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Bin Wei, Wen, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltan, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimaki, Terho, Study, Lifelines Cohort, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Poiasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Gauderman, W. James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., and Levy, Daniel
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
Published: 2018
Full Text: View/download PDF

46. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author: Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuhnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L., Canouil, Mickael, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, Fuentes, Lisa de las, de Mutsert, Renee, de Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelos, Fau, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charles, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Magi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, NelsonNona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thomas, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, Andre G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Bin Wei, Wen, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltan, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimaki, Terho, Study, Lifelines Cohort, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Poiasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Gauderman, W. James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., Levy, Daniel, Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuhnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L., Canouil, Mickael, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, Fuentes, Lisa de las, de Mutsert, Renee, de Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelos, Fau, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charles, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Magi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, NelsonNona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thomas, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, Andre G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Bin Wei, Wen, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltan, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimaki, Terho, Study, Lifelines Cohort, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Poiasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Gauderman, W. James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., and Levy, Daniel
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
Published: 2018
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47. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Author: Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpelainen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugues, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pires, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Kuhnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian' an, McKenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Debette, Stephanie, Dorr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charles, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charles, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Magi, Reedik, Mahajan, Anubha, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Jr., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Ultterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Bin Wei, Wen, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Kritchevsky, Stephen B., Levy, Daniel, O'Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpelainen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugues, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pires, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Kuhnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian' an, McKenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Debette, Stephanie, Dorr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charles, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charles, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Magi, Reedik, Mahajan, Anubha, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Jr., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Ultterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Bin Wei, Wen, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Kritchevsky, Stephen B., Levy, Daniel, O'Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., and Chasman, Daniel I.
Abstract: Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).
Published: 2018
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48. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Author: Feitosa, Mary F, Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M, Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Vitart, Veronique, Wang, Yajuan, Ware, Erin B, Warren, Helen R, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L, Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Ida Chen, Yii-Der, Connell, John M, Correa, Adolfo, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B, Ehret, Georg, Feitosa, Mary F, Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M, Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Vitart, Veronique, Wang, Yajuan, Ware, Erin B, Warren, Helen R, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L, Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Ida Chen, Yii-Der, Connell, John M, Correa, Adolfo, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B, and Ehret, Georg
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
Published: 2018

49. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Author: Feitosa, Mary F, Kuivaniemi, Helena1, Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M, Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Vitart, Veronique, Wang, Yajuan, Ware, Erin B, Warren, Helen R, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L, Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Ida Chen, Yii-Der, Connell, John M, Correa, Adolfo, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B, Ehret, Georg, Feitosa, Mary F, Kuivaniemi, Helena1, Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M, Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Vitart, Veronique, Wang, Yajuan, Ware, Erin B, Warren, Helen R, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L, Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Ida Chen, Yii-Der, Connell, John M, Correa, Adolfo, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B, and Ehret, Georg
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
Published: 2018

50. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author: Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea R V R, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Zhao, Jing Hua, Kilpeläinen, Tuomas O., Christensen, Kaare, V Varga, Tibor, Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea R V R, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Zhao, Jing Hua, Kilpeläinen, Tuomas O., Christensen, Kaare, and V Varga, Tibor
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
Published: 2018

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