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1. Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension

Author

Kelly, Tanika N, Sun, Xiao, He, Karen Y, Brown, Michael R, Taliun, Sarah A Gagliano, Hellwege, Jacklyn N, Irvin, Marguerite R, Mi, Xuenan, Brody, Jennifer A, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul S, Gao, Yan, Moscati, Arden, Nadkarni, Girish N, Yanek, Lisa R, Elfassy, Tali, Smith, Jennifer A, Chung, Ren-Hua, Beitelshees, Amber L, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon M, Peralta, Juan M, Assimes, Themistocles L, Palmas, Walter R, Liu, Chunyu, Bress, Adam P, Huang, Zhijie, Becker, Lewis C, Hwa, Chii-Min, O’Connell, Jeffrey R, Carlson, Jenna C, Warren, Helen R, Das, Sayantan, Giri, Ayush, Martin, Lisa W, Johnson, W Craig, Fox, Ervin R, Bottinger, Erwin P, Razavi, Alexander C, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei C, Naseri, Take, Jain, Deepti, Kang, Hyun Min, Hung, Adriana M, Srinivasasainagendra, Vinodh, Snively, Beverly M, Gu, Dongfeng, Montasser, May E, Reupena, Muagututi A Sefuiva, Heavner, Benjamin D, LeFaive, Jonathon, Hixson, James E, Rice, Kenneth M, Wang, Fei Fei, Nielsen, Jonas B, Huang, Jianfeng, Khan, Alyna T, Zhou, Wei, Nierenberg, Jovia L, Laurie, Cathy C, Armstrong, Nicole D, Shi, Mengyao, Pan, Yang, Stilp, Adrienne M, Emery, Leslie, Wong, Quenna, Hawley, Nicola L, Minster, Ryan L, Curran, Joanne E, Munroe, Patricia B, Weeks, Daniel E, North, Kari E, Tracy, Russell P, Kenny, Eimear E, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen S, Reiner, Alex P, Blangero, John, Redline, Susan, Mitchell, Braxton D, Rao, Dabeeru C, Chen, Yii-Der Ida, Kardia, Sharon LR, Kaplan, Robert C, Mathias, Rasika A, He, Jiang, Psaty, Bruce M, Fornage, Myriam, Loos, Ruth JF, Correa, Adolfo, Boerwinkle, Eric, Rotter, Jerome I, Kooperberg, Charles, and Edwards, Todd L

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Good Health and Well Being, Blood Pressure, Genome-Wide Association Study, Genomics, Humans, Hypertension, Polymorphism, Single Nucleotide, Precision Medicine, allele, blood pressure, genome, hypertension, whole genome sequencing, Samoan Obesity, Lifestyle, and Genetic Adaptations Study (OLaGA) Group, ‡ NHLBI Trans-Omics for Precision Medicine TOPMed) Consortium, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundThe availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.MethodsWe conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.ResultsTwo blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P

Published
2022

2. Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Author

Nakao, Tetsushi, Bick, Alexander G, Taub, Margaret A, Zekavat, Seyedeh M, Uddin, Md M, Niroula, Abhishek, Carty, Cara L, Lane, John, Honigberg, Michael C, Weinstock, Joshua S, Pampana, Akhil, Gibson, Christopher J, Griffin, Gabriel K, Clarke, Shoa L, Bhattacharya, Romit, Assimes, Themistocles L, Emery, Leslie S, Stilp, Adrienne M, Wong, Quenna, Broome, Jai, Laurie, Cecelia A, Khan, Alyna T, Smith, Albert V, Blackwell, Thomas W, Codd, Veryan, Nelson, Christopher P, Yoneda, Zachary T, Peralta, Juan M, Bowden, Donald W, Irvin, Marguerite R, Boorgula, Meher, Zhao, Wei, Yanek, Lisa R, Wiggins, Kerri L, Hixson, James E, Gu, C Charles, Peloso, Gina M, Roden, Dan M, Reupena, Muagututi’a S, Hwu, Chii-Min, DeMeo, Dawn L, North, Kari E, Kelly, Shannon, Musani, Solomon K, Bis, Joshua C, Lloyd-Jones, Donald M, Johnsen, Jill M, Preuss, Michael, Tracy, Russell P, Peyser, Patricia A, Qiao, Dandi, Desai, Pinkal, Curran, Joanne E, Freedman, Barry I, Tiwari, Hemant K, Chavan, Sameer, Smith, Jennifer A, Smith, Nicholas L, Kelly, Tanika N, Hidalgo, Bertha, Cupples, L Adrienne, Weeks, Daniel E, Hawley, Nicola L, Minster, Ryan L, Deka, Ranjan, Naseri, Take T, de las Fuentes, Lisa, Raffield, Laura M, Morrison, Alanna C, Vries, Paul S, Ballantyne, Christie M, Kenny, Eimear E, Rich, Stephen S, Whitsel, Eric A, Cho, Michael H, Shoemaker, M Benjamin, Pace, Betty S, Blangero, John, Palmer, Nicholette D, Mitchell, Braxton D, Shuldiner, Alan R, Barnes, Kathleen C, Redline, Susan, Kardia, Sharon LR, Abecasis, Gonçalo R, Becker, Lewis C, Heckbert, Susan R, He, Jiang, Post, Wendy, Arnett, Donna K, Vasan, Ramachandran S, Darbar, Dawood, Weiss, Scott T, McGarvey, Stephen T, de Andrade, Mariza, Chen, Yii-Der Ida, Kaplan, Robert C, Meyers, Deborah A, Custer, Brian S, and Correa, Adolfo

Subjects
Cardiovascular, Genetics, Aging, Heart Disease, Heart Disease - Coronary Heart Disease, Human Genome, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

Published
2022

3. Inherited causes of clonal haematopoiesis in 97,691 whole genomes

Author

Bick, Alexander G, Weinstock, Joshua S, Nandakumar, Satish K, Fulco, Charles P, Bao, Erik L, Zekavat, Seyedeh M, Szeto, Mindy D, Liao, Xiaotian, Leventhal, Matthew J, Nasser, Joseph, Chang, Kyle, Laurie, Cecelia, Burugula, Bala Bharathi, Gibson, Christopher J, Niroula, Abhishek, Lin, Amy E, Taub, Margaret A, Aguet, Francois, Ardlie, Kristin, Mitchell, Braxton D, Barnes, Kathleen C, Moscati, Arden, Fornage, Myriam, Redline, Susan, Psaty, Bruce M, Silverman, Edwin K, Weiss, Scott T, Palmer, Nicholette D, Vasan, Ramachandran S, Burchard, Esteban G, Kardia, Sharon LR, He, Jiang, Kaplan, Robert C, Smith, Nicholas L, Arnett, Donna K, Schwartz, David A, Correa, Adolfo, de Andrade, Mariza, Guo, Xiuqing, Konkle, Barbara A, Custer, Brian, Peralta, Juan M, Gui, Hongsheng, Meyers, Deborah A, McGarvey, Stephen T, Chen, Ida Yii-Der, Shoemaker, M Benjamin, Peyser, Patricia A, Broome, Jai G, Gogarten, Stephanie M, Wang, Fei Fei, Wong, Quenna, Montasser, May E, Daya, Michelle, Kenny, Eimear E, North, Kari E, Launer, Lenore J, Cade, Brian E, Bis, Joshua C, Cho, Michael H, Lasky-Su, Jessica, Bowden, Donald W, Cupples, L Adrienne, Mak, Angel CY, Becker, Lewis C, Smith, Jennifer A, Kelly, Tanika N, Aslibekyan, Stella, Heckbert, Susan R, Tiwari, Hemant K, Yang, Ivana V, Heit, John A, Lubitz, Steven A, Johnsen, Jill M, Curran, Joanne E, Wenzel, Sally E, Weeks, Daniel E, Rao, Dabeeru C, Darbar, Dawood, Moon, Jee-Young, Tracy, Russell P, Buth, Erin J, Rafaels, Nicholas, Loos, Ruth JF, Durda, Peter, Liu, Yongmei, Hou, Lifang, Lee, Jiwon, Kachroo, Priyadarshini, Freedman, Barry I, Levy, Daniel, Bielak, Lawrence F, Hixson, James E, Floyd, James S, Whitsel, Eric A, Ellinor, Patrick T, Irvin, Marguerite R, Fingerlin, Tasha E, Raffield, Laura M, and Armasu, Sebastian M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biotechnology, Regenerative Medicine, Stem Cell Research, Human Genome, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Cardiovascular, Generic health relevance, Inflammatory and immune system, Good Health and Well Being, Adult, Africa, Aged, Aged, 80 and over, Black People, Cell Self Renewal, Clonal Hematopoiesis, DNA-Binding Proteins, Dioxygenases, Female, Genetic Predisposition to Disease, Genome, Human, Germ-Line Mutation, Hematopoietic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Precision Medicine, Proto-Oncogene Proteins, Tripartite Motif Proteins, United States, Whole Genome Sequencing, alpha Karyopherins, NHLBI Trans-Omics for Precision Medicine Consortium, General Science & Technology
Abstract

Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer2-4 and coronary heart disease5-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)6. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues.

Published
2020

4. 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 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

Subjects
Humans, Lipids, Chromosome Mapping, Sleep, Phylogeny, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Genetic Loci, Polymorphism, Single Nucleotide, and over
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

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

Author

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

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Biotechnology, Genetics, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Asian People, Blood Pressure, Asia, Eastern, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Phenotype, Polymorphism, Single Nucleotide, arterial pressure, blood pressure, epidemiology, genome-wide association study, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
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

Published
2017

6. Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference.

Author

Wen, Wanqing, Kato, Norihiro, Hwang, Joo-Yeon, Guo, Xingyi, Tabara, Yasuharu, Li, Huaixing, Dorajoo, Rajkumar, Yang, Xiaobo, Tsai, Fuu-Jen, Li, Shengxu, Wu, Ying, Wu, Tangchun, Kim, Soriul, Guo, Xiuqing, Liang, Jun, Shungin, Dmitry, Adair, Linda S, Akiyama, Koichi, Allison, Matthew, Cai, Qiuyin, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Yuan-Tsong, Cho, Yoon Shin, Choi, Bo Youl, Gao, Yutang, Go, Min Jin, Gu, Dongfeng, Han, Bok-Ghee, He, Meian, Hixson, James E, Hu, Yanling, Huang, Tao, Isono, Masato, Jung, Keum Ji, Kang, Daehee, Kim, Young Jin, Kita, Yoshikuni, Lee, Juyoung, Lee, Nanette R, Lee, Jeannette, Wang, Yiqin, Liu, Jian-Jun, Long, Jirong, Moon, Sanghoon, Nakamura, Yasuyuki, Nakatochi, Masahiro, Ohnaka, Keizo, Rao, Dabeeru, Shi, Jiajun, Sull, Jae Woong, Tan, Aihua, Ueshima, Hirotsugu, Wu, Chen, Xiang, Yong-Bing, Yamamoto, Ken, Yao, Jie, Ye, Xingwang, Yokota, Mitsuhiro, Zhang, Xiaomin, Zheng, Yan, Qi, Lu, Rotter, Jerome I, Jee, Sun Ha, Lin, Dongxin, Mohlke, Karen L, He, Jiang, Mo, Zengnan, Wu, Jer-Yuarn, Tai, E Shyong, Lin, Xu, Miki, Tetsuro, Kim, Bong-Jo, Takeuchi, Fumihiko, Zheng, Wei, and Shu, Xiao-Ou

Subjects
Humans, Obesity, Genetic Predisposition to Disease, Waist-Hip Ratio, Sex Factors, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Asian Continental Ancestry Group, Asia, Female, Male, Waist Circumference, Genome-Wide Association Study, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Clinical Research, Genetics, 2.1 Biological and endogenous factors, Cardiovascular, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.

Published
2016

8. Meta-analysis identifies multiple loci associated with kidney function–related traits in east Asian populations

Author

Okada, Yukinori, Sim, Xueling, Go, Min Jin, Wu, Jer-Yuarn, Gu, Dongfeng, Takeuchi, Fumihiko, Takahashi, Atsushi, Maeda, Shiro, Tsunoda, Tatsuhiko, Chen, Peng, Lim, Su-Chi, Wong, Tien-Yin, Liu, Jianjun, Young, Terri L, Aung, Tin, Seielstad, Mark, Teo, Yik-Ying, Kim, Young Jin, Lee, Jong-Young, Han, Bok-Ghee, Kang, Daehee, Chen, Chien-Hsiun, Tsai, Fuu-Jen, Chang, Li-Ching, Fann, S-J Cathy, Mei, Hao, Rao, Dabeeru C, Hixson, James E, Chen, Shufeng, Katsuya, Tomohiro, Isono, Masato, Ogihara, Toshio, Chambers, John C, Zhang, Weihua, Kooner, Jaspal S, Albrecht, Eva, Yamamoto, Kazuhiko, Kubo, Michiaki, Nakamura, Yusuke, Kamatani, Naoyuki, Kato, Norihiro, He, Jiang, Chen, Yuan-Tsong, Cho, Yoon Shin, Tai, E-Shyong, and Tanaka, Toshihiro

Subjects
Biological Sciences, Genetics, Kidney Disease, Human Genome, Renal and urogenital, Asian People, Blood Urea Nitrogen, Cohort Studies, Creatinine, Genetic Predisposition to Disease, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic, Uric Acid, KidneyGen Consortium, CKDGen Consortium, GUGC consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

Published
2012

10. Assessment of postprandial triglycerides in clinical practice: Validation in a general population and coronary heart disease patients

Author

Perez-Martinez, Pablo, Alcala-Diaz, Juan F., Kabagambe, Edmon K., Garcia-Rios, Antonio, Tsai, Michael Y., Delgado-Lista, Javier, Kolovou, Genovefa, Straka, Robert J., Gomez-Delgado, Francisco, Hopkins, Paul N., Marin, Carmen, Borecki, Ingrid, Yubero-Serrano, Elena M., Hixson, James E., Camargo, Antonio, Province, Michael A., Lopez-Moreno, Javier, Rodriguez-Cantalejo, Fernando, Tinahones, Francisco J., Mikhailidis, Dimitri P., Perez-Jimenez, Francisco, Arnett, Donna K., Ordovas, Jose M., and Lopez-Miranda, Jose

Published
2016
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11. Proteomic Architecture of Human Coronary and Aortic Atherosclerosis

Author

Herrington, David M., Mao, Chunhong, Parker, Sarah J., Fu, Zongming, Yu, Guoqiang, Chen, Lulu, Venkatraman, Vidya, Fu, Yi, Wang, Yizhi, Howard, Timothy D., Jun, Goo, Zhao, Caroline F., Liu, Yongmei, Saylor, Georgia, Spivia, Weston R., Athas, Grace B., Troxclair, Dana, Hixson, James E., Vander Heide, Richard S., Wang, Yue, and Van Eyk, Jennifer E.

Published
2018
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15. Whole-exome sequencing study identifies four novel gene loci associated with diabetic kidney disease.

Author

Pan, Yang, Sun, Xiao, Mi, Xuenan, Huang, Zhijie, Hsu, Yenchih, Hixson, James E, Munzy, Donna, Metcalf, Ginger, Franceschini, Nora, Tin, Adrienne, Köttgen, Anna, Francis, Michael, Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium TOPMed Kidney Function Working, Brody, Jennifer A, Kestenbaum, Bryan, Sitlani, Colleen M, Mychaleckyj, Josyf C, Kramer, Holly, Lange, Leslie A, and Guo, Xiuqing

Published
2023
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20. Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension

Author

Lu, Xiangfeng, Wang, Laiyuan, Lin, Xu, Huang, Jianfeng, Charles Gu, C., He, Meian, Shen, Hongbing, He, Jiang, Zhu, Jingwen, Li, Huaixing, Hixson, James E., Wu, Tangchun, Dai, Juncheng, Lu, Ling, Shen, Chong, Chen, Shufeng, He, Lin, Mo, Zengnan, Hao, Yongchen, Mo, Xingbo, Yang, Xueli, Li, Jianxin, Cao, Jie, Chen, Jichun, Fan, Zhongjie, Li, Ying, Zhao, Liancheng, Li, Hongfan, Lu, Fanghong, Yao, Cailiang, Yu, Lin, Xu, Lihua, Mu, Jianjun, Wu, Xianping, Deng, Ying, Hu, Dongsheng, Zhang, Weidong, Ji, Xu, Guo, Dongshuang, Guo, Zhirong, Zhou, Zhengyuan, Yang, Zili, Wang, Renping, Yang, Jun, Zhou, Xiaoyang, Yan, Weili, Sun, Ningling, Gao, Pingjin, and Gu, Dongfeng

Published
2015
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21. Genome-Wide Association Meta-analysis Identifies Novel Variants Associated With Fasting Plasma Glucose in East Asians

Author

Hwang, Joo-Yeon, Sim, Xueling, Wu, Ying, Liang, Jun, Tabara, Yasuharu, Hu, Cheng, Hara, Kazuo, Tam, Claudia H.T., Cai, Qiuyin, Zhao, Qi, Jee, Sunha, Takeuchi, Fumihiko, Go, Min Jin, Ong, Rick Twee Hee, Ohkubo, Takayoshi, Kim, Young Jin, Zhang, Rong, Yamauchi, Toshimasa, So, Wing Yee, Long, Jirong, Gu, Dongfeng, Lee, Nanette R., Kim, Soriul, Katsuya, Tomohiro, Oh, Ji Hee, Liu, Jianjun, Umemura, Satoshi, Kim, Yeon-Jung, Jiang, Feng, Maeda, Shiro, Chan, Juliana C.N., Lu, Wei, Hixson, James E., Adair, Linda S., Jung, Keum Ji, Nabika, Toru, Bae, Jae-Bum, Lee, Mi Hee, Seielstad, Mark, Young, Terri L., Teo, Yik Ying, Kita, Yoshikuni, Takashima, Naoyuki, Osawa, Haruhiko, Lee, So-Hyun, Shin, Min-Ho, Shin, Dong Hoon, Choi, Bo Youl, Shi, Jiajun, Gao, Yu-Tang, Xiang, Yong-Bing, Zheng, Wei, Kato, Norihiro, Yoon, Miwuk, He, Jiang, Shu, Xiao Ou, Ma, Ronald C.W., Kadowaki, Takashi, Jia, Weiping, Miki, Tetsuro, Qi, Lu, Tai, E Shyong, Mohlke, Karen L., Han, Bok-Ghee, Cho, Yoon Shin, and Kim, Bong-Jo

Published
2015
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27. Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia

Author

Warodomwichit, Daruneewan, Arnett, Donna K., Kabagambe, Edmond K., Tsai, Michael Y., Hixson, James E., Straka, Robert J., Province, Michael, An, Ping, Lai, Chao-Qiang, Borecki, Ingrid, and Ordovas, Jose M.

Subjects
Unsaturated fatty acids -- Health aspects, Unsaturated fatty acids -- Genetic aspects, Lipemia -- Genetic aspects, DNA binding proteins -- Health aspects, Single nucleotide polymorphisms -- Health aspects, Metabolic syndrome X -- Genetic aspects, Genetic variation -- Research, Food/cooking/nutrition
Abstract

The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCFTL2 locus on postprandial lipemia and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the C/T rs7903146 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of [beta] cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.007) concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and PUFA intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P = 0.018) concentrations. Thus, only T allele carriers with a PUFA intake [greater than or equal to] 7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in T allele carriers and noncarriers in the low-PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes ([greater than or equal to] 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease.

Published
2009

29. Interleukin 1[beta] genetic polymorphisms interact with polyunsaturated fatty acids to modulate risk of the metabolic syndrome

Author

Shen, Jian, Arnett, Donna K., Peacock, James M., Parnell, Laurence D., Kraja, Aldi, Hixson, James E., Tsai, Michael Y., Lai, Chao-Qiang, Kabagambe, Edmond K., Straka, Robert J., and Ordovas, Jose M.

Subjects
Metabolic syndrome X -- Genetic aspects, Metabolic syndrome X -- Diet therapy, Metabolic syndrome X -- Physiological aspects, Metabolic syndrome X -- Chemical properties, Interleukin-1 -- Physiological aspects, Interleukin-1 -- Genetic aspects, Genetic polymorphisms -- Physiological aspects, Genetic polymorphisms -- Chemical properties, Unsaturated fatty acids -- Physiological aspects, Food/cooking/nutrition
Abstract

Chronic inflammation has been identified as an important component of the metabolic syndrome (MetS). Therefore, environmental and genetic factors contributing to the variation of inflammatory responses could affect individuals' susceptibility to MetS. We investigated the association between common IL 1[beta] genetic polymorphisms, inflammation, and the MetS, and the modulation of diet-related variables (i.e., erythrocyte membrane fatty acid composition) in a white U.S. population. IL 1[beta] single nucleotide polymorphisms (SNP) (-1473G > C, 511G > A, -31T > C, 3966C > T, 6054G > A), clinical and biochemical measurements were characterized in a total of 1120 subjects (540 males and 580 females) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. The 6054 G > A SNP was significantly associated with plasma C-reactive protein (P = 0.054), adiponectin (P=0.021), and the prevalence of MetS (P = 0.004). Moreover, there was a significant interaction between the 6054G > A SNP and erythrocyte membrane (n-3) PUFA (P = 0.019). Among subjects with low (n-3) PUFA content (below the median), the 6054 G allele was associated with increased risk of the MetS (OR = 3.29, 95%Cl = 1.49-7.26 for GG and OR = 1.95, 95%Cl = 0.854.46 for GA, P < 0.001) compared with the AA genotype, but there were no significant genotype associations among subjects with high (n-3) PUFA content (above the median). Further analyses supported a significant haplotype global effect on the MetS (P = 0.017) among subjects with low (n-3) PUFA content. These results suggested that IL 1[beta] genetic variants were associated with measures of chronic inflammation and the MetS risk, and that genetic influences were more evident among subjects with low (n-3) PUFA intake.

Published
2007

34. Human pedigree-based quantitative-trait-locus mapping: localization of two genes influencing HDL-cholesterol metabolism

Author

Almasy, Laura, Hixson, James E., Rainwater, David L., Cole, Shelley, Williams, Jeff T., Mahaney, Michael C., VandeBerg, John L., Stern, Michael P., MacCluer, Jean W., and Blangero, John

Subjects
Cholesterol metabolism -- Genetic aspects, Cholesterol, HDL -- Physiological aspects, Biological sciences
Abstract

Genes located on chromosome 8 and chromosome 15 appear to influence HLD-cholesterol metabolism., according to results of a full genomic scan. Multivariate analyses indicate that the locus on chromosome 8 affects unesterified cholesterol levels, while the locus on chromosome 15 affects concentration of HDL-cholesterol as well as how cholesterol is distributed among different particle sizes of HDL. Data were derived from Mexican American families in the San Antonio Family Heart Study.

Published
1999

35. Genetics of atherosclerosis risk factors in Mexican Americans

Author

MacCluer, Jean W., Stern, Michael P., Almasy, Laura, Atwood, Larry A., Blangero, John, Comuzzie, Anthony G., Dyke, Bennett, Haffner, Steven M., Henkel, Richard D., Hixson, James E., Kammerer, Candace M., Mahaney, Michael C., Mitchell, Braxton D., Rainwater, David L., Samollow, Paul B., Sharp, R. Mark, VandeBerg, John L., and Williams, Jeff T.

Subjects
Atherosclerosis -- Risk factors, Mexican Americans -- Diseases, Heart diseases -- Patient outcomes, Food/cooking/nutrition
Abstract

Genes contribute to the high risk of heart disease in Mexican Americans. A study of 1,400 people from 42 extended Mexican-American families localized some genetic evidence for disease risk. Researchers determined the chromosomal locations for risk factor genes linked to atherosclerosis, obesity, and diabetes. There were genetic effects on leptin and HDL-C levels. Largely unknown new genes were identified for 13 major disease traits.

Published
1999

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, He, Meian, Horimoto, Andrea RVR, 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 YQ, 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, Sr, Wilson Gregory, 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 KE, Oldehinkel, Albertine J, Penninx, Brenda WJH, 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 LR, 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 JF, 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, Consortium, COGENT-Kidney, Consortium, EPIC-InterAct, Grp, Understanding Soc Sci, Cohort, Lifelines, National Institutes of Health [Bethesda] (NIH), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), The University of Texas Health Science Center at Houston (UTHealth), Universität Regensburg (UR), Queen Mary University of London (QMUL), Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Public Health [Boston], Boston University [Boston] (BU), Los Angeles Biomedical Research Institute (LA BioMed), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Singapore Eye Research Institute [Singapore] (SERI), Duke-NUS Medical School [Singapore], National University of Singapore (NUS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Edinburgh, University of Mississippi Medical Center (UMMC), University of Georgia [USA], Leiden University Medical Center (LUMC), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Harvard T.H. Chan School of Public Health, University of Washington [Seattle], Wake Forest University, Genome Institute of Singapore (GIS), Massachusetts General Hospital [Boston], Pennington Biomedical Research Center, Louisiana State University (LSU), Icelandic Heart Association [Kopavogur, Iceland] (IHA), University of Iceland [Reykjavik], University of Michigan [Ann Arbor], University of Michigan System, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Tartu, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Imperial College London, University of Ioannina, University of Oxford [Oxford], University of Groningen [Groningen], Universidade Federal de Pelotas = Federal University of Pelotas (UFPel), University of Bristol [Bristol], Huazhong University of Science and Technology [Wuhan] (HUST), Universidade de São Paulo Medical School (FMUSP), Case Western Reserve University [Cleveland], University of Southern California (USC), This project was largely supported by a grant from the US National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL118305) and by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health through the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362)., Bentley, Ar, Sung, Yj, Brown, Mr, Winkler, Tw, Kraja, At, Ntalla, I, Schwander, K, Chasman, Di, Lim, E, Deng, X, Guo, X, Liu, J, Lu, Y, Cheng, Cy, Sim, X, Vojinovic, D, Huffman, Je, Musani, Sk, Li, C, Feitosa, Mf, Richard, Ma, Noordam, R, Baker, J, Chen, G, Aschard, H, Bartz, Tm, Ding, J, Dorajoo, R, Manning, Ak, Rankinen, T, Smith, Av, Tajuddin, Sm, Zhao, W, Graff, M, Alver, M, Boissel, M, Chai, Jf, Chen, X, Divers, J, Evangelou, E, Gao, C, Goel, A, Hagemeijer, Y, Harris, Se, Hartwig, Fp, He, M, Horimoto, Arvr, Hsu, Fc, Hung, Yj, Jackson, Au, Kasturiratne, A, Komulainen, P, Kühnel, B, Leander, K, Lin, Kh, Luan, J, Lyytikäinen, Lp, Matoba, N, Nolte, Im, Pietzner, M, Prins, B, Riaz, M, Robino, A, Said, Ma, Schupf, N, Scott, Ra, Sofer, T, Stancáková, A, Takeuchi, F, Tayo, Bo, van der Most, Pj, Varga, Tv, Wang, Td, Wang, Y, Ware, Eb, Wen, W, Xiang, Yb, Yanek, Lr, Zhang, W, Zhao, Jh, Adeyemo, A, Afaq, S, Amin, N, Amini, M, Arking, De, Arzumanyan, Z, Aung, T, Ballantyne, C, Barr, Rg, Bielak, Lf, Boerwinkle, E, Bottinger, Ep, Broeckel, U, Brown, M, Cade, Be, Campbell, A, Canouil, M, Charumathi, S, Chen, Yi, Christensen, K, COGENT-Kidney, Consortium, Concas, Mp, Connell, Jm, de Las Fuentes, L, de Silva, Hj, de Vries, P, Doumatey, A, Duan, Q, Eaton, Cb, Eppinga, Rn, Faul, Jd, Floyd, J, Forouhi, Ng, Forrester, T, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, M, Gharib, Sa, Gigante, B, Giulianini, F, Grabe, Hj, Gu, Cc, Harris, Tb, Heikkinen, S, Heng, Ck, Hirata, M, Hixson, Je, Ikram, Ma, EPIC-InterAct, Consortium, Jia, Y, Joehanes, R, Johnson, C, Jonas, Jb, Justice, Ae, Katsuya, T, Khor, Cc, Kilpeläinen, To, Koh, Wp, Kolcic, I, Kooperberg, C, Krieger, Je, Kritchevsky, Sb, Kubo, M, Kuusisto, J, Lakka, Ta, Langefeld, Cd, Langenberg, C, Launer, Lj, Lehne, B, Lewis, Ce, Li, Y, Liang, J, Lin, S, Liu, Ct, Liu, K, Loh, M, Lohman, Kk, Louie, T, Luzzi, A, Mägi, R, Mahajan, A, Manichaikul, Aw, Mckenzie, Ca, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, Kl, Momozawa, Y, Morris, Ap, Murray, Ad, Nalls, Ma, Nauck, M, Nelson, Cp, North, Ke, O'Connell, Jr, Palmer, Nd, Papanicolau, Gj, Pedersen, Nl, Peters, A, Peyser, Pa, Polasek, O, Poulter, N, Raitakari, Ot, Reiner, Ap, Renström, F, Rice, Tk, Rich, S, Robinson, Jg, Rose, Lm, Rosendaal, Fr, Rudan, I, Schmidt, Co, Schreiner, Pj, Scott, Wr, Sever, P, Shi, Y, Sidney, S, Sims, M, Smith, Ja, Snieder, H, Starr, Jm, Strauch, K, Stringham, Hm, Tan, Nyq, Tang, H, Taylor, Kd, Teo, Yy, Tham, Yc, Tiemeier, H, Turner, St, Uitterlinden, Ag, Understanding Society Scientific, Group, van Heemst, D, Waldenberger, M, Wang, H, Wang, L, Wei, Wb, Williams, Ca, Wilson, G Sr, Wojczynski, Mk, Yao, J, Young, K, Yu, C, Yuan, Jm, Zhou, J, Zonderman, Ab, Becker, Dm, Boehnke, M, Bowden, Dw, Chambers, Jc, Cooper, R, de Faire, U, Deary, Ij, Elliott, P, Esko, T, Farrall, M, Franks, Pw, Freedman, Bi, Froguel, P, Gasparini, P, Gieger, C, Horta, Bl, Juang, Jj, Kamatani, Y, Kammerer, Cm, Kato, N, Kooner, J, Laakso, M, Laurie, Cc, Lee, It, Lehtimäki, T, Lifelines, Cohort, Magnusson, Pke, Oldehinkel, Aj, Penninx, Bwjh, Pereira, Ac, Rauramaa, R, Redline, S, Samani, Nj, Scott, J, Shu, Xo, van der Harst, P, Wagenknecht, Le, Wang, J, Wang, Yx, Wareham, Nj, Watkins, H, Weir, Dr, Wickremasinghe, Ar, Wu, T, Zeggini, E, Zheng, W, Bouchard, C, Evans, Mk, Gudnason, V, Kardia, Slr, Liu, Y, Psaty, Bm, Ridker, Pm, van Dam, Rm, Mook-Kanamori, Do, Fornage, M, Province, Ma, Kelly, Tn, Fox, Er, Hayward, C, van Duijn, Cm, Tai, E, Wong, Ty, Loos, Rjf, Franceschini, N, Rotter, Ji, Zhu, X, Bierut, Lj, Gauderman, Wj, Rice, K, Munroe, Pb, Morrison, Ac, Rao, Dc, Rotimi, Cn, Cupples, La., Luan, Jian'an [0000-0003-3137-6337], Pietzner, Maik [0000-0003-3437-9963], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Home Office, Action on Hearing Loss, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), Universiteit Leiden, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), University of Oxford, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, and APH - Digital Health

Subjects
Male, Linkage disequilibrium, Blood lipids, Genome-wide association study, VARIANTS, SUSCEPTIBILITY, Environment interaction, Genome, Linkage Disequilibrium, MESH: Genotype, 0302 clinical medicine, MESH: Aged, 80 and over, Genotype, NICOTINE METABOLISM, 11 Medical and Health Sciences, Genetics & Heredity, Aged, 80 and over, Genetics, MESH: Aged, 0303 health sciences, ARCHITECTURE, [STAT.AP]Statistics [stat]/Applications [stat.AP], Genotype imputation, MESH: Middle Aged, CHOLESTEROL, Smoking, MESH: Life Style, Lifelines Cohort, Middle Aged, Lipids, 3. Good health, ENVIRONMENT INTERACTION, GENOTYPE IMPUTATION, RISK LOCI, METAANALYSIS, CIGARETTES, Cholesterol, MESH: Linkage Disequilibrium, MESH: Young Adult, Meta-analysis, Genome-Wide Association Study/methods, Smoking/blood, Medical genetics, Female, EPIC-InterAct Consortium, Life Sciences & Biomedicine, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Adult, Metaanalysi, Understanding Society Scientific Group, medicine.medical_specialty, MESH: Smoking, Adolescent, Genomics, COGENT-Kidney Consortium, Biology, Nicotine metabolism, Risk loci, Metaanalysis, Cigarettes, Article, Young Adult, 03 medical and health sciences, genomics, medicine, Humans, Linkage Disequilibrium/genetics, Life Style, Aged, 030304 developmental biology, MESH: Adolescent, Science & Technology, MESH: Humans, Lipids/blood, MESH: Adult, 06 Biological Sciences, MESH: Lipids, MESH: Male, cardiovascular diseases, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, genome-wide association studies, MESH: Genome-Wide Association Study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
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 novel loci, some of which were detected only because the association differed by smoking status. Additionally, we demonstrated 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., Editorial summary: A multi-ancestry genome-wide gene-smoking interaction study identifies 13 new loci associated with serum lipids.

Published
2019

42. 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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43. 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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44. Discovery of a brain promoter from the human transferrin gene and its utilization for development of transgenic mice that express human apolipoprotein E alleles

Author

Bowman, Barbara H., Jansen, Laila, Yang, Funmei, Adrian, Gwendolyn S., Zhao, Ming, Atherton, Sally S., Buchanan, James M., Greene, Rhonda, Walter, Christi, Herbert, Damon C., Weaker, Frank J., Chiodo, Laura K., Kagan-Hallet, Kathleen, and Hixson, James E.

Subjects
Brain -- Physiological aspects, Transferrin -- Genetic aspects, Apolipoproteins -- Genetic aspects, Genetically modified mice -- Genetic aspects, Science and technology
Abstract

A study was conducted to characterize the intracellular brain protein from the human transferrin (TF) gene and examine its role in the expression of human apolipoprotein E alleles in transgenic mice. Engineered plasmids identified the protein as chloramphenicol acetyltransferase (CAT) while southern blot analysis was used to identify the TF-CAT gene in transgenic mouse. The results of the study are discussed.

Published
1995

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