Functionally oriented analysis of cardiometabolic traits in a trans-ethnic sample

被引：10

作者：

Petty, Lauren E. ^{[1
,2
]}

Highland, Heather M. ^{[2
,3
]}

Gamazon, Eric R. ^{[1
,4
]}

Hu, Hao ^{[5
]}

Karhade, Mandar ^{[2
]}

Chen, Hung-Hsin ^{[1
,2
]}

de Vries, Paul S. ^{[2
]}

Grove, Megan L. ^{[2
]}

Aguilar, David ^{[6
]}

Bell, Graeme I. ^{[7
,8
]}

Huff, Chad D. ^{[5
]}

Hanis, Craig L. ^{[2
]}

Doddapaneni, HarshaVardhan ^{[9
]}

Munzy, Donna M. ^{[9
]}

Gibbs, Richard A. ^{[9
]}

Ma, Jianzhong ^{[2
]}

Parra, Esteban J. ^{[10
]}

Cruz, Miguel ^{[11
]}

Valladares-Salgado, Adan ^{[11
]}

Arking, Dan E. ^{[12
]}

Barbeira, Alvaro ^{[13
]}

Im, Hae Kyung ^{[13
]}

Morrison, Alanna C. ^{[2
]}

Boerwinkle, Eric ^{[2
]}

Below, Jennifer E. ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, 221 Kirkland Hall, Nashville, TN 37235 USA

[2] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA

[3] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[4] Univ Cambridge, Clare Hall, Cambridge, England

[5] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[6] Baylor Coll Med, Dept Cardiol, Houston, TX 77030 USA

[7] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA

[8] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[9] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[10] Univ Toronto, Dept Anthropol, Mississauga, ON, Canada

[11] Hosp Especialidades Ctr Med La Raza, Ctr Med Nacl Siglo 21, IMSS, Unidad Invest Med Bioquim, Mexico City, DF, Mexico

[12] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[13] Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA

来源：

HUMAN MOLECULAR GENETICS | 2019年 / 28卷 / 07期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL; L GENE-CLUSTER; DNA METHYLATION; COMPLEX TRAITS; LOW-FREQUENCY; FACTOR-VII; VARIANTS; EXPRESSION; BLOOD;

D O I：

10.1093/hmg/ddy435

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interpretation of genetic association results is difficult because signals often lack biological context. To generate hypotheses of the functional genetic etiology of complex cardiometabolic traits, we estimated the genetically determined component of gene expression from common variants using PrediXcan (I) and determined genes with differential predicted expression by trait. PrediXcan imputes tissue-specific expression levels from genetic variation using variant-level effect on gene expression in transcriptome data. To explore the value of imputed genetically regulated gene expression (GReX) models across different ancestral populations, we evaluated imputed expression levels for predictive accuracy genome-wide in RNA sequence data in samples drawn from European-ancestry and African-ancestry populations and identified substantial predictive power using European-derived models in a non-European target population. We then tested the association of GReX on 15 cardiometabolic traits including blood lipid levels, body mass index, height, blood pressure, fasting glucose and insulin, RR interval, fibrinogen level, factor VII level and white blood cell and platelet counts in 15 755 individuals across three ancestry groups, resulting in 20 novel gene-phenotype associations reaching experiment-wide significance across ancestries. In addition, we identified 18 significant novel gene-phenotype associations in our ancestry-specific analyses. Top associations were assessed for additional support via query of S-PrediXcan (2) results derived from publicly available genome-wide association studies summary data. Collectively, these findings illustrate the utility of transcriptome-based imputation models for discovery of cardiometabolic effect genes in a diverse dataset.

引用

页码：1212 / 1224

页数：13

共 50 条

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Graham, Nicholas ;

Ferguson, Amy ;

Johnston, Keira J. A. ;

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[28] Trans-ethnic association study of blood pressure determinants in over 750,000 individuals [J].

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Wilson, Otis D. ;

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Arnett, Donna K. ;

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Liang, Shuang ;

Siscovick, David S. ;

Tsai, Michael Y. ;

Rich, Stephen S. ;

Fornage, Myriam ;

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Rimm, Eric B. ;

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← 1 2 3 4 5 →

共 50 条

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Liu, Li ;

Wen, Yan ;

Ning, Yujie ;

Li, Ping ;

Cheng, Bolun ;

Cheng, Shiqiang ;

Zhang, Lu ;

Ma, Mei ;

Qi, Xin ;

Liang, Chujun ;

Yang, Tielin ;

Chen, Xiangding ;

Tan, Lijun ;

Shen, Hui ;

Tian, Qing ;

Deng, Hong-Wen ;

Ma, Xiancang ;

Zhang, Feng ;

Zhu, Feng .

CLINICAL AND TRANSLATIONAL MEDICINE, 2020, 9 (01)

[22] Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained [J].

Wu, Ying ;

Waite, Lindsay L. ;

Jackson, Anne U. ;

Sheu, Wayne H-H. ;

Buyske, Steven ;

Absher, Devin ;

Arnett, Donna K. ;

Boerwinkle, Eric ;

Bonnycastle, Lori L. ;

Carty, Cara L. ;

Cheng, Iona ;

Cochran, Barbara ;

Croteau-Chonka, Damien C. ;

Dumitrescu, Logan ;

Eaton, Charles B. ;

Franceschini, Nora ;

Guo, Xiuqing ;

Henderson, Brian E. ;

Hindorff, Lucia A. ;

Kim, Eric ;

Kinnunen, Leena ;

Komulainen, Pirjo ;

Lee, Wen-Jane ;

Le Marchand, Loic ;

Lin, Yi ;

Lindstrom, Jaana ;

Lingaas-Holmen, Oddgeir ;

Mitchell, Sabrina L. ;

Narisu, Narisu ;

Robinson, Jennifer G. ;

Schumacher, Fred ;

Stancakova, Alena ;

Sundvall, Jouko ;

Sung, Yun-Ju ;

Swift, Amy J. ;

Wang, Wen-Chang ;

Wilkens, Lynne ;

Wilsgaard, Tom ;

Young, Alicia M. ;

Adair, Linda S. ;

Ballantyne, Christie M. ;

Buzkova, Petra ;

Chakravarti, Aravinda ;

Collins, Francis S. ;

Duggan, David ;

Feranil, Alan B. ;

Ho, Low-Tone ;

Hung, Yi-Jen ;

Hunt, Steven C. ;

Hveem, Kristian .

PLOS GENETICS, 2013, 9 (03)

[23] Trans-ethnic follow-up of breast cancer GWAS hits using the preferential linkage disequilibrium approach [J].

Zhu, Qianqian ;

Shepherd, Lori ;

Lunetta, Kathryn L. ;

Yao, Song ;

Liu, Qian ;

Hu, Qiang ;

Haddad, Stephen A. ;

Sucheston-Campbell, Lara ;

Bensen, Jeannette T. ;

Bandera, Elisa V. ;

Rosenberg, Lynn ;

Liu, Song ;

Haiman, Christopher A. ;

Olshan, Andrew F. ;

Palmer, Julie R. ;

Ambrosone, Christine B. .

ONCOTARGET, 2016, 7 (50) :83160-83176

[24] Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci [J].

Charles E. Breeze ;

Anna Batorsky ;

Mi Kyeong Lee ;

Mindy D. Szeto ;

Xiaoguang Xu ;

Daniel L. McCartney ;

Rong Jiang ;

Amit Patki ;

Holly J. Kramer ;

James M. Eales ;

Laura Raffield ;

Leslie Lange ;

Ethan Lange ;

Peter Durda ;

Yongmei Liu ;

Russ P. Tracy ;

David Van Den Berg ;

Kathryn L. Evans ;

William E. Kraus ;

Svati Shah ;

Hermant K. Tiwari ;

Lifang Hou ;

Eric A. Whitsel ;

Xiao Jiang ;

Fadi J. Charchar ;

Andrea A. Baccarelli ;

Stephen S. Rich ;

Andrew P. Morris ;

Marguerite R. Irvin ;

Donna K. Arnett ;

Elizabeth R. Hauser ;

Jerome I. Rotter ;

Adolfo Correa ;

Caroline Hayward ;

Steve Horvath ;

Riccardo E. Marioni ;

Maciej Tomaszewski ;

Stephan Beck ;

Sonja I. Berndt ;

Stephanie J. London ;

Josyf C. Mychaleckyj ;

Nora Franceschini .

Genome Medicine, 13

[25] Large trans-ethnic meta-analysis identifies AKRIC4 as a novel gene associated with age at menarche [J].

Sarnowski, C. ;

Cousminer, D. L. ;

Franceschini, N. ;

Raffield, L. M. ;

Jia, G. ;

Fernandez-Rhodes, L. ;

Grant, S. F. A. ;

Hakonarson, H. ;

Lange, L. A. ;

Long, J. ;

Sofer, T. ;

Tao, R. ;

Wallace, R. B. ;

Wong, Q. ;

Zirpoli, G. ;

Boerwinkle, E. ;

Bradfield, J. P. ;

Correa, A. ;

Kooperberg, C. L. ;

North, K. E. ;

Palmer, J. R. ;

Zemel, B. S. ;

Zheng, W. ;

Murabito, J. M. ;

Lunetta, K. L. .

HUMAN REPRODUCTION, 2021, 36 (07) :1999-2010

[26] Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity [J].

Mahajan, Anubha ;

Rodan, Aylin R. ;

Le, Thu H. ;

Gaulton, Kyle J. ;

Haessler, Jeffrey ;

Stilp, Adrienne M. ;

Kamatani, Yoichiro ;

Zhu, Gu ;

Sofer, Tamar ;

Puri, Sanjana ;

Schellinger, Jeffrey N. ;

Chu, Pei-Lun ;

Cechova, Sylvia ;

van Zuydam, Natalie ;

Arnlov, Johan ;

Flessner, Michael F. ;

Giedraitis, Vilmantas ;

Heath, Andrew C. ;

Kubo, Michiaki ;

Larsson, Anders ;

Lindgren, Cecilia M. ;

Madden, Pamela A. F. ;

Montgomery, Grant W. ;

Papanicolaou, George J. ;

Reiner, Alex P. ;

Sundstrom, Johan ;

Thornton, Timothy A. ;

Lind, Lars ;

Ingelsson, Erik ;

Cai, Jianwen ;

Martin, Nicholas G. ;

Kooperberg, Charles ;

Matsuda, Koichi ;

Whitfield, John B. ;

Okada, Yukinori ;

Laurie, Cathy C. ;

Morris, Andrew P. ;

Franceschini, Nora .

AMERICAN JOURNAL OF HUMAN GENETICS, 2016, 99 (03) :636-646

[27] Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression [J].

Strawbridge, Rona J. ;

Ward, Joey ;

Lyall, Laura M. ;

Tunbridge, Elizabeth M. ;

Cullen, Breda ;

Graham, Nicholas ;

Ferguson, Amy ;

Johnston, Keira J. A. ;

Lyall, Donald M. ;

Mackay, Daniel ;

Cavanagh, Jonathan ;

Howard, David M. ;

Adams, Mark J. ;

Deary, Ian ;

Escott-Price, Valentina ;

O'Donovan, Michael ;

McIntosh, Andrew M. ;

Bailey, Mark E. S. ;

Pell, Jill P. ;

Harrison, Paul J. ;

Smith, Daniel J. .

TRANSLATIONAL PSYCHIATRY, 2018, 8

[28] Trans-ethnic association study of blood pressure determinants in over 750,000 individuals [J].

Giri, Ayush ;

Hellwege, Jacklyn N. ;

Keaton, Jacob M. ;

Park, Jihwan ;

Qiu, Chengxiang ;

Warren, Helen R. ;

Torstenson, Eric S. ;

Kovesdy, Csaba P. ;

Sun, Yan V. ;

Wilson, Otis D. ;

Robinson-Cohen, Cassianne ;

Roumie, Christianne L. ;

Chung, Cecilia P. ;

Birdwell, Kelly A. ;

Damrauer, Scott M. ;

DuVall, Scott L. ;

Klarin, Derek ;

Cho, Kelly ;

Wang, Yu ;

Evangelou, Evangelos ;

Cabrera, Claudia P. ;

Wain, Louise V. ;

Shrestha, Rojesh ;

Mautz, Brian S. ;

Akwo, Elvis A. ;

Sargurupremraj, Muralidharan ;

Debette, Stephanie ;

Boehnke, Michael ;

Scott, Laura J. ;

Luan, Jian'an ;

Zhao, Jing-Hua ;

Willems, Sara M. ;

Theriault, Sebastien ;

Shah, Nabi ;

Oldmeadow, Christopher ;

Almgren, Peter ;

Li-Gao, Ruifang ;

Verweij, Niek ;

Boutin, Thibaud S. ;

Mangino, Massimo ;

Ntalla, Ioanna ;

Feofanova, Elena ;

Surendran, Praveen ;

Cook, James P. ;

Karthikeyan, Savita ;

Lahrouchi, Najim ;

Liu, Chunyu ;

Sepulveda, Nuno ;

Richardson, Tom G. ;

Kraja, Aldi .

NATURE GENETICS, 2019, 51 (01) :51-+

[29] Genome-wide trans-ethnic meta-analysis identifies novel susceptibility loci for childhood acute lymphoblastic leukemia [J].

Jeon, Soyoung ;

de Smith, Adam J. ;

Li, Shaobo ;

Chen, Minhui ;

Chan, Tsz Fung ;

Muskens, Ivo S. ;

Morimoto, Libby M. ;

DeWan, Andrew T. ;

Mancuso, Nicholas ;

Metayer, Catherine ;

Ma, Xiaomei ;

Wiemels, Joseph L. ;

Chiang, Charleston W. K. .

LEUKEMIA, 2022, 36 (03) :865-868

[30] Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations [J].

Hu, Yao ;

Tanaka, Toshiko ;

Zhu, Jingwen ;

Guan, Weihua ;

Wu, Jason H. Y. ;

Psaty, Bruce M. ;

McKnight, Barbara ;

King, Irena B. ;

Sun, Qi ;

Richard, Melissa ;

Manichaikul, Ani ;

Frazier-Wood, Alexis C. ;

Kabagambe, Edmond K. ;

Hopkins, Paul N. ;

Ordovas, Jose M. ;

Ferrucci, Luigi ;

Bandinelli, Stefania ;

Arnett, Donna K. ;

Chen, Yii-Der I. ;

Liang, Shuang ;

Siscovick, David S. ;

Tsai, Michael Y. ;

Rich, Stephen S. ;

Fornage, Myriam ;

Hu, Frank B. ;

Rimm, Eric B. ;

Jensen, Majken K. ;

Lemaitre, Rozenn N. ;

Mozaffarian, Dariush ;

Steffen, Lyn M. ;

Morris, Andrew P. ;

Li, Huaixing ;

Lin, Xu .

JOURNAL OF LIPID RESEARCH, 2017, 58 (05) :974-981

← 1 2 3 4 5 →