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4. Supplementary Figure and Table from Genetic Variability of Smoking Persistence in African Americans

Author

Hamidovic, Ajna, primary, Kasberger, John L., primary, Young, Taylor R., primary, Goodloe, Robert J., primary, Redline, Susan, primary, Buxbaum, Sarah G., primary, Benowitz, Neal L., primary, Bergen, Andrew W., primary, Butler, Kenneth R., primary, Franceschini, Nora, primary, Gharib, Sina A., primary, Hitsman, Brian, primary, Levy, Daniel, primary, Meng, Yan, primary, Papanicolaou, George J., primary, Preis, Sarah R., primary, Spring, Bonnie, primary, Styn, Mindi A., primary, Tong, Elisa K., primary, White, Wendy B., primary, Wiggins, Kerri L., primary, and Jorgenson, Eric, primary

Published
2023
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5. Data from Genetic Variability of Smoking Persistence in African Americans

Author

Hamidovic, Ajna, primary, Kasberger, John L., primary, Young, Taylor R., primary, Goodloe, Robert J., primary, Redline, Susan, primary, Buxbaum, Sarah G., primary, Benowitz, Neal L., primary, Bergen, Andrew W., primary, Butler, Kenneth R., primary, Franceschini, Nora, primary, Gharib, Sina A., primary, Hitsman, Brian, primary, Levy, Daniel, primary, Meng, Yan, primary, Papanicolaou, George J., primary, Preis, Sarah R., primary, Spring, Bonnie, primary, Styn, Mindi A., primary, Tong, Elisa K., primary, White, Wendy B., primary, Wiggins, Kerri L., primary, and Jorgenson, Eric, primary

Published
2023
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6. The human transcriptome across tissues and individuals

Author

The GTEx Consortium, Melé, Marta, Ferreira, Pedro G., Reverter, Ferran, DeLuca, David S., Monlong, Jean, Sammeth, Michael, Young, Taylor R., Goldmann, Jakob M, Pervouchine, Dmitri D., Sullivan, Timothy J., Johnson, Rory, Segrè, Ayellet V., Djebali, Sarah, Niarchou, Anastasia, Wright, Fred A., Lappalainen, Tuuli, Calvo, Miquel, Getz, Gad, Dermitzakis, Emmanouil T., Ardlie, Kristin G., and Guigó, Roderic

Published
2015

8. HUMAN GENOMICS: The human transcriptome across tissues and individuals

Author

Melé, Marta, Ferreira, Pedro G., Reverter, Ferran, DeLuca, David S., Monlong, Jean, Sammeth, Michael, Young, Taylor R., M Goldmann, Jakob, Pervouchine, Dmitri D., Sullivan, Timothy J., Johnson, Rory, Segrè, Ayellet V., Djebali, Sarah, Niarchou, Anastasia, Wright, Fred A., Lappalainen, Tuuli, Calvo, Miquel, Getz, Gad, Dermitzakis, Emmanouil T., Ardlie, Kristin G., and Guigó, Roderic

Published
2015
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9. Replication and fine mapping of asthma-associated loci in individuals of African ancestry

Author

Kantor, David B., Palmer, Cameron D., Young, Taylor R., Meng, Yan, Gajdos, Zofia K., Lyon, Helen, Price, Alkes L., Pollack, Samuela, London, Stephanie J., Loehr, Laura R., Smith, Lewis J., Kumar, Rajesh, Jacobs Jr., David R., Petrini, Marcy F., O’Connor, George T., White, Wendy B., Papanicolaou, George, Burkart, Kristin M., Heckbert, Susan R., Barr, R. Graham, and Hirschhorn, Joel N.

Published
2013
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10. A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project

Author

Broad Institute of MIT and Harvard, Ardlie, Kristin G., DeLuca, David S., Gelfand, Ellen T., Segre, Ayellet V., Young, Taylor R., GTex Consortium, Broad Institute of MIT and Harvard, Ardlie, Kristin G., DeLuca, David S., Gelfand, Ellen T., Segre, Ayellet V., Young, Taylor R., and GTex Consortium

Abstract

© Copyright 2015, Mary Ann Liebert, Inc. 2015. The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community., National Institutes of Health (Grant HHSN261200800001E)

Published
2021

11. APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema

Author

Burke, Gregory L., Watson, Karol, Tobin, Martin D., Tsai, Michael Y., Ahmed, Firas S., Petrini, Marcy, Hoffman, Eric A., O'Connor, George T., Young, Taylor R., Manichaikul, Ani, London, Stephanie J., Redline, Susan, Smith, Lewis J., Burkart, Kristin M., Artigas, María Soler, Barr, R. Graham, Meng, Yang, Oelsner, Elizabeth, Enright, Paul, Wilk, Jemma B., Haynes, Demondes, Heckbert, Susan R., Hansel, Nadia N., Rotter, Jerome I., Kaufman, Joel D., Pottinger, Tess D., Rich, Stephen S., Loehr, Laura, Powell, Charles A., Kurai, Jun, and White, Wendy

Subjects
respiratory tract diseases
Abstract

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD.

Published
2014
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12. APOM and High-Density Lipoprotein are associated with Lung Function and Percent Emphysema

Author

Burkart, Kristin M, Manichaikul, Ani, Wilk, Jemma B, Ahmed, Firas S, Burke, Gregory L, Enright, Paul, Hansel, Nadia N, Haynes, Demondes, Heckbert, Susan R, Hoffman, Eric A, Kaufman, Joel D, Kurai, Jun, Loehr, Laura, London, Stephanie J, Meng, Yang, O’Connor, George T, Oelsner, Elizabeth, Petrini, Marcy, Pottinger, Tess D, Powell, Charles A, Redline, Susan, Rotter, Jerome I, Smith, Lewis J, Artigas, María Soler, Tobin, Martin D, Tsai, Michael Y, Watson, Karol, White, Wendy, Young, Taylor R, Rich, Stephen S, and Barr, R Graham

Subjects
Adult, Male, Genotype, Vital Capacity, Apolipoproteins M, Polymorphism, Single Nucleotide, Article, White People, Cohort Studies, Pulmonary Disease, Chronic Obstructive, Forced Expiratory Volume, Humans, Lung, Aged, Emphysema, Gene Expression Profiling, Cholesterol, HDL, Middle Aged, Lipocalins, United States, respiratory tract diseases, Black or African American, Apolipoproteins, Gene Expression Regulation, Spirometry, Female
Abstract

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10(-7)). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

Published
2013

13. The human transcriptome across tissues and individuals

Author

Melé, Marta, primary, Ferreira, Pedro G., additional, Reverter, Ferran, additional, DeLuca, David S., additional, Monlong, Jean, additional, Sammeth, Michael, additional, Young, Taylor R., additional, Goldmann, Jakob M, additional, Pervouchine, Dmitri D., additional, Sullivan, Timothy J., additional, Johnson, Rory, additional, Segrè, Ayellet V., additional, Djebali, Sarah, additional, Niarchou, Anastasia, additional, Consortium, The GTEx, additional, Wright, Fred A., additional, Lappalainen, Tuuli, additional, Calvo, Miquel, additional, Getz, Gad, additional, Dermitzakis, Emmanouil T., additional, Ardlie, Kristin G., additional, and Guigó, Roderic, additional

Published
2015
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14. Genetic variability of smoking persistence in African Americans.

Author

Hamidovic, Ajna, Hamidovic, Ajna, Kasberger, John L, Young, Taylor R, Goodloe, Robert J, Redline, Susan, Buxbaum, Sarah G, Benowitz, Neal L, Bergen, Andrew W, Butler, Kenneth R, Franceschini, Nora, Gharib, Sina A, Hitsman, Brian, Levy, Daniel, Meng, Yan, Papanicolaou, George J, Preis, Sarah R, Spring, Bonnie, Styn, Mindi A, Tong, Elisa K, White, Wendy B, Wiggins, Kerri L, Jorgenson, Eric, Hamidovic, Ajna, Hamidovic, Ajna, Kasberger, John L, Young, Taylor R, Goodloe, Robert J, Redline, Susan, Buxbaum, Sarah G, Benowitz, Neal L, Bergen, Andrew W, Butler, Kenneth R, Franceschini, Nora, Gharib, Sina A, Hitsman, Brian, Levy, Daniel, Meng, Yan, Papanicolaou, George J, Preis, Sarah R, Spring, Bonnie, Styn, Mindi A, Tong, Elisa K, White, Wendy B, Wiggins, Kerri L, and Jorgenson, Eric

Abstract

To date, most genetic association analyses of smoking behaviors have been conducted in populations of European ancestry and many of these studies focused on the phenotype that measures smoking quantity, that is, cigarettes per day. Additional association studies in diverse populations with different linkage disequilibrium patterns and an alternate phenotype, such as total tobacco exposure which accounts for intermittent periods of smoking cessation within a larger smoking period as measured in large cardiovascular risk studies, can aid the search for variants relevant to smoking behavior. For these reasons, we undertook an association analysis by using a genotyping array that includes 2,100 genes to analyze smoking persistence in unrelated African American participants from the Atherosclerosis Risk in Communities study. A locus located approximately 4 kb downstream from the 3'-UTR of the brain-derived neurotrophic factor (BDNF) significantly influenced smoking persistence. In addition, independent variants rs12915366 and rs12914385 in the cluster of genes encoding nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4) on 15q25.1 were also associated with the phenotype in this sample of African American subjects. To our knowledge, this is the first study to more extensively evaluate the genome in the African American population, as a limited number of previous studies of smoking behavior in this population included evaluations of only single genomic regions.

Published
2011

15. Genetic Analysis of a Population Heavy Drinking Phenotype Identifies Risk Variants in Whites

Author

Hamidovic, Ajna, primary, Goodloe, Robert J., additional, Young, Taylor R., additional, Styn, Mindi A., additional, Mukamal, Kenneth J., additional, Choquet, Helene, additional, Kasberger, Jay L., additional, Buxbaum, Sarah G., additional, Papanicolaou, George J., additional, White, Wendy, additional, Volcik, Kelly, additional, Spring, Bonnie, additional, Hitsman, Brian, additional, Levy, Daniel, additional, and Jorgenson, Eric, additional

Published
2013
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16. Gene-Centric Analysis of Serum Cotinine Levels in African and European American Populations

Author

Hamidovic, Ajna, primary, Goodloe, Robert J, additional, Bergen, Andrew W, additional, Benowitz, Neal L, additional, Styn, Mindi A, additional, Kasberger, Jay L, additional, Choquet, Helene, additional, Young, Taylor R, additional, Meng, Yan, additional, Palmer, Cameron, additional, Pletcher, Mark, additional, Kertesz, Stefan, additional, Hitsman, Brian, additional, Spring, Bonnie, additional, and Jorgenson, Eric, additional

Published
2011
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17. Genetic Variability of Smoking Persistence in African Americans

Author

Hamidovic, Ajna, primary, Kasberger, John L., additional, Young, Taylor R., additional, Goodloe, Robert J., additional, Redline, Susan, additional, Buxbaum, Sarah G., additional, Benowitz, Neal L., additional, Bergen, Andrew W., additional, Butler, Kenneth R., additional, Franceschini, Nora, additional, Gharib, Sina A., additional, Hitsman, Brian, additional, Levy, Daniel, additional, Meng, Yan, additional, Papanicolaou, George J., additional, Preis, Sarah R., additional, Spring, Bonnie, additional, Styn, Mindi A., additional, Tong, Elisa K., additional, White, Wendy B., additional, Wiggins, Kerri L., additional, and Jorgenson, Eric, additional

Published
2011
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18. Gene-Centric Analysis of Serum Cotinine Levels in African and European American Populations.

Author

Hamidovic, Ajna, Goodloe, Robert J, Bergen, Andrew W, Benowitz, Neal L, Styn, Mindi A, Kasberger, Jay L, Choquet, Helene, Young, Taylor R, Meng, Yan, Palmer, Cameron, Pletcher, Mark, Kertesz, Stefan, Hitsman, Brian, Spring, Bonnie, and Jorgenson, Eric

Subjects
COTININE, SMOKING, SERUM, GENOTYPE-environment interaction, EUROPEAN Americans, AFRICAN Americans
Abstract

To date, most genetic association studies of tobacco use have been conducted in European American subjects using the phenotype of smoking quantity (cigarettes per day). However, smoking quantity is a very imprecise measure of exposure to tobacco smoke constituents. Analyses of alternate phenotypes and populations may improve our understanding of tobacco addiction genetics. Cotinine is the major metabolite of nicotine, and measuring serum cotinine levels in smokers provides a more objective measure of nicotine dose than smoking quantity. Previous genetic association studies of serum cotinine have focused on individual genes. We conducted a genetic association study of the biomarker in African American (N=365) and European American (N=315) subjects from the Coronary Artery Risk Development in Young Adults study using a chip containing densely-spaced tag SNPs in ∼2100 genes. We found that rs11187065, located in the non-coding region (intron 1) of insulin-degrading enzyme (IDE), was the most strongly associated SNP (p=8.91 × 10−6) in the African American cohort, whereas rs11763963, located on chromosome 7 outside of a gene transcript, was the most strongly associated SNP in European Americans (p=1.53 × 10−6). We then evaluated how the top variant association in each population performed in the other group. We found that the association of rs11187065 in IDE was also associated with the phenotype in European Americans (p=0.044). Our top SNP association in European Americans, rs11763963 was non-polymorphic in our African American sample. It has been previously shown that psychostimulant self-administration is reduced in animals with lower insulin because of interference with dopamine transmission in the brain reward centers. Our finding provides a platform for further investigation of this, or additional mechanisms, involving the relationship between insulin and self-administered nicotine dose. [ABSTRACT FROM AUTHOR]

Published
2012
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19. Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies IL6R Polymorphism in Relation to Atrial Fibrillation.

Author

Schnabel, Renate B., Kerr, Kathleen F., Lubitz, Steven A., Alkylbekova, Ermeg L., Marcus, Gregory M., Sinner, Moritz F., Magnani, Jared W., Wolf, Philip A., Deo, Rajat, Lloyd-Jones, Donald M., Lunetta, Kathryn L., Mehra, Reena, Levy, Daniel, Fox, Ervin R., Arking, Dan E., Mosley, Thomas H., Müller-Nurasyid, Martina, Young, Taylor R., Wichmann, H.-Erich, and Seshadri, Sudha

Abstract

The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.We examined a panel of approximately 50 000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18 524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19 602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence interval [CI], 0.85-0.95; P=0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72-1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57-0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16-1.69; P=0.0005).In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans. [ABSTRACT FROM AUTHOR]

Published
2011
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20. Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

Author

Yang, Jialiang, Huang, Tao, Petralia, Francesca, Long, Quan, Zhang, Bin, Argmann, Carmen, Zhao, Yong, Mobbs, Charles V., Schadt, Eric E., Zhu, Jun, Tu, Zhidong, Ardlie, Kristin G., Deluca, David S., Segrè, Ayellet V., Sullivan, Timothy J., Young, Taylor R., Gelfand, Ellen T., Trowbridge, Casandra A., Maller, Julian B., Tukiainen, Taru, Lek, Monkol, Ward, Lucas D., Kheradpour, Pouya, Iriarte, Benjamin, Meng, Yan, Palmer, Cameron D., Winckler, Wendy, Hirschhorn, Joel, Kellis, Manolis, MacArthur, Daniel G., Getz, Gad, Shablin, Andrey A., Li, Gen, Zhou, Yi-Hui, Nobel, Andrew B., Rusyn, Ivan, Wright, Fred A., Lappalainen, Tuuli, Ferreira, Pedro G., Ongen, Halit, Rivas, Manuel A., Battle, Alexis, Mostafavi, Sara, Monlong, Jean, Sammeth, Michael, Mele, Marta, Reverter, Ferran, Goldman, Jakob, Koller, Daphne, Guigo, Roderic, McCarthy, Mark I., Dermitzakis, Emmanouil T., Gamazon, Eric R., Konkashbaev, Anuar, Nicolae, Dan L., Cox, Nancy J., Flutre, Timothée, Wen, Xiaoquan, Stephens, Matthew, Pritchard, Jonathan K., Lin, Luan, Liu, Jun, Brown, Amanda, Mestichelli, Bernadette, Tidwell, Denee, Lo, Edmund, Salvatore, Mike, Shad, Saboor, Thomas, Jeffrey A., Lonsdale, John T., Choi, Christopher, Karasik, Ellen, Ramsey, Kimberly, Moser, Michael T., Foster, Barbara A., Gillard, Bryan M., Syron, John, Fleming, Johnelle, Magazine, Harold, Hasz, Rick, Walters, Gary D., Bridge, Jason P., Miklos, Mark, Sullivan, Susan, Barker, Laura K., Traino, Heather, Mosavel, Magboeba, Siminoff, Laura A., Valley, Dana R., Rohrer, Daniel C., Jewel, Scott, Branton, Philip, Sobin, Leslie H., Qi, Liqun, Hariharan, Pushpa, Wu, Shenpei, Tabor, David, Shive, Charles, Smith, Anna M., Buia, Stephen A., Undale, Anita H., Robinson, Karna L., Roche, Nancy, Valentino, Kimberly M., Britton, Angela, Burges, Robin, Bradbury, Debra, Hambright, Kenneth W., Seleski, John, Korzeniewski, Greg E., Erickson, Kenyon, Marcus, Yvonne, Tejada, Jorge, Taherian, Mehran, Lu, Chunrong, Robles, Barnaby E., Basile, Margaret, Mash, Deborah C., Volpi, Simona, Struewing, Jeff, Temple, Gary F., Boyer, Joy, Colantuoni, Deborah, Little, Roger, Koester, Susan, Carithers, NCI Latarsha J., Moore, Helen M., Guan, Ping, Compton, Carolyn, Sawyer, Sherilyn J., Demchok, Joanne P., Vaught, Jimmie B., Rabiner, Chana A., and Lockhart, Nicole C.

Abstract

Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger “co-aging” than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.

Published
2015
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21. Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies IL6RPolymorphism in Relation to Atrial Fibrillation

Author

Schnabel, Renate B., Kerr, Kathleen F., Lubitz, Steven A., Alkylbekova, Ermeg L., Marcus, Gregory M., Sinner, Moritz F., Magnani, Jared W., Wolf, Philip A., Deo, Rajat, Lloyd-Jones, Donald M., Lunetta, Kathryn L., Mehra, Reena, Levy, Daniel, Fox, Ervin R., Arking, Dan E., Mosley, Thomas H., Müller-Nurasyid, Martina, Young, Taylor R., Wichmann, H.-Erich, Seshadri, Sudha, Farlow, Deborah N., Rotter, Jerome I., Soliman, Elsayed Z., Glazer, Nicole L., Wilson, James G., Breteler, Monique M.B., Sotoodehnia, Nona, Newton-Cheh, Christopher, Kääb, Stefan, Ellinor, Patrick T., Alonso, Alvaro, Benjamin, Emelia J., and Heckbert, Susan R.

Abstract

The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.

Published
2011
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22. A Meta-Analysis Identifies New Loci Associated with Body Mass index in Individuals of African Ancestry

Author

Monda, Keri L., Chen, Gary K., Taylor, Kira C., Palmer, Cameron, Edwards, Todd L., Lange, Leslie A., Ng, Maggie C.Y., Adeyemo, Adebowale A., Allison, Matthew A., Bielak, Lawrence F., Chen, Guanji, Graff, Mariaelisa, Irvin, Marguerite R., Rhie, Suhn K., Li, Guo, Liu, Yongmei, Liu, Youfang, Lu, Yingchang, Nalls, Michael A., Sun, Yan V., Wojczynski, Mary K., Yanek, Lisa R., Aldrich, Melinda C., Ademola, Adeyinka, Amos, Christopher I., Bandera, Elisa V., Bock, Cathryn H., Britton, Angela, Broeckel, Ulrich, Cai, Quiyin, Caporaso, Neil E., Carlson, Chris, Carpten, John, Casey, Graham, Chen, Wei-Min, Chen, Fang, Chen, Yii-Der I., Chiang, Charleston W.K., Coetzee, Gerhard A., Demerath, Ellen, Deming-Halverson, Sandra L., Driver, Ryan W., Dubbert, Patricia, Feitosa, Mary F., Freedman, Barry I., Gillanders, Elizabeth M., Gottesman, Omri, Guo, Xiuqing, Haritunians, Talin, Harris, Tamara, Harris, Curtis C., Hennis, Anselm JM, Hernandez, Dena G., McNeill, Lorna H., Howard, Timothy D., Howard, Barbara V., Howard, Virginia J., Johnson, Karen C., Kang, Sun J., Keating, Brendan J., Kolb, Suzanne, Kuller, Lewis H., Kutlar, Abdullah, Langefeld, Carl D., Lettre, Guillaume, Lohman, Kurt, Lotay, Vaneet, Lyon, Helen, Manson, JoAnn E., Maixner, William, Meng, Yan A., Monroe, Kristine R., Morhason-Bello, Imran, Murphy, Adam B., Mychaleckyj, Josyf C., Nadukuru, Rajiv, Nathanson, Katherine L., Nayak, Uma, N’Diaye, Amidou, Nemesure, Barbara, Wu, Suh-Yuh, Leske, M. Cristina, Neslund-Dudas, Christine, Neuhouser, Marian, Nyante, Sarah, Ochs-Balcom, Heather, Ogunniyi, Adesola, Ogundiran, Temidayo O., Ojengbede, Oladosu, Olopade, Olufunmilayo I., Palmer, Julie R., Ruiz-Narvaez, Edward A., Palmer, Nicholette D., Press, Michael F., Rampersaud, Evandine, Rasmussen-Torvik, Laura J., Rodriguez-Gil, Jorge L., Salako, Babatunde, Schadt, Eric E., Schwartz, Ann G., Shriner, Daniel A., Siscovick, David, Smith, Shad B., Wassertheil-Smoller, Sylvia, Speliotes, Elizabeth K., Spitz, Margaret R., Sucheston, Lara, Taylor, Herman, Tayo, Bamidele O., Tucker, Margaret A., Van Den Berg, David J., Velez Edwards, Digna R., Wang, Zhaoming, Wiencke, John K., Winkler, Thomas W., Witte, John S., Wrensch, Margaret, Wu, Xifeng, Yang, James J., Levin, Albert M., Young, Taylor R., Zakai, Neil A., Cushman, Mary, Zanetti, Krista A., Zhao, Jing Hua, Zhao, Wei, Zheng, Yonglan, Zhou, Jie, Ziegler, Regina G., Zmuda, Joseph M., Fernandes, Jyotika K., Gilkeson, Gary S., Kamen, Diane L., Hunt, Kelly J., Spruill, Ida J., Ambrosone, Christine B., Ambs, Stefan, Arnett, Donna K., Atwood, Larry, Becker, Diane M., Berndt, Sonja I., Bernstein, Leslie, Blot, William J., Borecki, Ingrid B., Bottinger, Erwin P., Bowden, Donald W., Burke, Gregory, Chanock, Stephen J., Cooper, Richard S., Ding, Jingzhong, Duggan, David, Evans, Michele K., Fox, Caroline, Garvey, W. Timothy, Bradfield, Jonathan P., Hakonarson, Hakon, Grant, Struan F.A., Hsing, Ann, Chu, Lisa, Hu, Jennifer J., Huo, Dezheng, Ingles, Sue A., John, Esther M., Jordan, Joanne M., Kabagambe, Edmond K., Kardia, Sharon L.R., Kittles, Rick A., Goodman, Phyllis J., Klein, Eric A., Kolonel, Laurence N., Le Marchand, Loic, Liu, Simin, McKnight, Barbara, Millikan, Robert C., Mosley, Thomas H., Padhukasahasram, Badri, Williams, L. Keoki, Patel, Sanjay R., Peters, Ulrike, Pettaway, Curtis A., Peyser, Patricia A., Psaty, Bruce M., Redline, Susan, Rotimi, Charles N., Rybicki, Benjamin A., Sale, Michèle M., Schreiner, Pamela J., Signorello, Lisa B., Singleton, Andrew B., Stanford, Janet L., Strom, Sara S., Thun, Michael J., Vitolins, Mara, Zheng, Wei, Moore, Jason H., Williams, Scott M., Zhu, Xiaofeng, Zonderman, Alan B., Kooperberg, Charles, Papanicolaou, George, Henderson, Brian E., Reiner, Alex P., Hirschhorn, Joel N., Loos, Ruth JF, North, Kari E., and Haiman, Christopher A.

Abstract

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations.

Published
2013
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23. Cyclonite-Induced Seizures After Voluntary C-4 Ingestion.

Author

Fang T, Karandikar PV, Young TR, and Umeton RP

Abstract

Cyclonite (cyclotrimethylenetrinitramine, RDX, hexogen) is the active agent in the plastic explosive, composition 4 (C-4). It has been used globally since the Vietnam War for both military and civilian applications due to its metastable nature. Ingestion or inhalation of C-4 can cause euphoric effects such as those commonly seen with alcohol toxicity, in addition to seizures and rarely fulminant liver and kidney failure. We report the case of a patient who ingested 75 g of C-4 and presented with a generalized tonic-clonic seizure four hours after ingestion. Our patient made a full recovery after being stabilized with temporizing anticonvulsants in the intensive care unit., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Fang et al.)

Published
2023
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24. A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project.

Author

Carithers LJ, Ardlie K, Barcus M, Branton PA, Britton A, Buia SA, Compton CC, DeLuca DS, Peter-Demchok J, Gelfand ET, Guan P, Korzeniewski GE, Lockhart NC, Rabiner CA, Rao AK, Robinson KL, Roche NV, Sawyer SJ, Segrè AV, Shive CE, Smith AM, Sobin LH, Undale AH, Valentino KM, Vaught J, Young TR, and Moore HM

Subjects
Humans, Biomedical Research methods, Biomedical Research organization & administration, Biomedical Research standards, Tissue Banks, Tissue and Organ Procurement methods, Tissue and Organ Procurement organization & administration, Tissue and Organ Procurement standards
Abstract

The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community.

Published
2015
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25. APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.

Author

Burkart KM, Manichaikul A, Wilk JB, Ahmed FS, Burke GL, Enright P, Hansel NN, Haynes D, Heckbert SR, Hoffman EA, Kaufman JD, Kurai J, Loehr L, London SJ, Meng Y, O'Connor GT, Oelsner E, Petrini M, Pottinger TD, Powell CA, Redline S, Rotter JI, Smith LJ, Soler Artigas M, Tobin MD, Tsai MY, Watson K, White W, Young TR, Rich SS, and Barr RG

Subjects
Adult, Black or African American, Aged, Apolipoproteins M, Cohort Studies, Female, Forced Expiratory Volume, Gene Expression Profiling, Gene Expression Regulation, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Spirometry, United States, Vital Capacity, White People, Apolipoproteins genetics, Cholesterol, HDL blood, Emphysema blood, Lipocalins genetics, Lung physiology, Pulmonary Disease, Chronic Obstructive blood
Abstract

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10(-7)). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

Published
2014
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