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2,001 results on '"Jensen, Richard A."'

1. Noisy Instance Removal Using OWA-Based Fuzzy-Rough Sets

Author

Jensen, Richard, Parthaláin, Neil Mac, Amiri, Mehran, Cassens, Jörg, Kacprzyk, Janusz, Series Editor, Pal, Nikhil R., Advisory Editor, Bello Perez, Rafael, Advisory Editor, Corchado, Emilio S., Advisory Editor, Hagras, Hani, Advisory Editor, Kóczy, László T., Advisory Editor, Kreinovich, Vladik, Advisory Editor, Lin, Chin-Teng, Advisory Editor, Lu, Jie, Advisory Editor, Melin, Patricia, Advisory Editor, Nedjah, Nadia, Advisory Editor, Nguyen, Ngoc Thanh, Advisory Editor, Wang, Jun, Advisory Editor, Panoutsos, George, editor, Mahfouf, Mahdi, editor, and Mihaylova, Lyudmila S, editor

Published
2024
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5. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Author

Mahajan, Anubha, Spracklen, Cassandra N, Zhang, Weihua, Ng, Maggie CY, Petty, Lauren E, Kitajima, Hidetoshi, Yu, Grace Z, Rüeger, Sina, Speidel, Leo, Kim, Young Jin, Horikoshi, Momoko, Mercader, Josep M, Taliun, Daniel, Moon, Sanghoon, Kwak, Soo-Heon, Robertson, Neil R, Rayner, Nigel W, Loh, Marie, Kim, Bong-Jo, Chiou, Joshua, Miguel-Escalada, Irene, della Briotta Parolo, Pietro, Lin, Kuang, Bragg, Fiona, Preuss, Michael H, Takeuchi, Fumihiko, Nano, Jana, Guo, Xiuqing, Lamri, Amel, Nakatochi, Masahiro, Scott, Robert A, Lee, Jung-Jin, Huerta-Chagoya, Alicia, Graff, Mariaelisa, Chai, Jin-Fang, Parra, Esteban J, Yao, Jie, Bielak, Lawrence F, Tabara, Yasuharu, Hai, Yang, Steinthorsdottir, Valgerdur, Cook, James P, Kals, Mart, Grarup, Niels, Schmidt, Ellen M, Pan, Ian, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloe, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Ahmad, Meraj, Noordam, Raymond, Lim, Victor JY, Tam, Claudia HT, Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M, Lecoeur, Cécile, Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R, Chen, Guanjie, Jensen, Richard A, Tajuddin, Salman, Kabagambe, Edmond K, An, Ping, Xiang, Anny H, Choi, Hyeok Sun, Cade, Brian E, Tan, Jingyi, Flanagan, Jack, Abaitua, Fernando, Adair, Linda S, Adeyemo, Adebowale, Aguilar-Salinas, Carlos A, Akiyama, Masato, Anand, Sonia S, Bertoni, Alain, Bian, Zheng, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A, Brummett, Chad M, Buchanan, Thomas A, Canouil, Mickaël, Chan, Juliana CN, Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, and Cushman, Mary

Subjects
Genetics, Diabetes, Human Genome, Metabolic and endocrine, Diabetes Mellitus, Type 2, Ethnicity, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors, FinnGen, eMERGE Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P 50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.

Published
2022

6. Gene Set Enrichment Analsyes Identiify Pathways Involved in Genetic Risk for Diabetic Retinopathy

Author

Sobrin, Lucia, Susarla, Gayatri, Stanwyck, Lynn, Rouhana, John M, Li, Ashley, Pollack, Samuela, Igo, Robert P, Jensen, Richard A, Li, Xiaohui, Ng, Maggie CY, Smith, Albert V, Kuo, Jane Z, Taylor, Kent D, Freedman, Barry I, Bowden, Donald W, Penman, Alan, Chen, Ching J, Craig, Jamie E, Adler, Sharon G, Chew, Emily Y, Cotch, Mary Frances, Yaspan, Brian, Mitchell, Paul, Wang, Jie Jin, Klein, Barbara EK, Wong, Tien Y, Rotter, Jerome I, Burdon, Kathyrn P, Iyengar, Sudha K, and Segrè, Ayellet V

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Diabetes, Genetics, Human Genome, 2.1 Biological and endogenous factors, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses.MethodsWe analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was

Published
2022

10. Multiethnic Genome-wide Association Study of Diabetic Retinopathy using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control

Author

Pollack, Samuela, Igo, Robert P, Jensen, Richard A, Christiansen, Mark, Li, Xiaohui, Cheng, Ching-Yu, Ng, Maggie CY, Smith, Albert V, Rossin, Elizabeth J, Segrè, Ayellet V, Davoudi, Samaneh, Tan, Gavin S, Chen, Yii-Der Ida, Kuo, Jane Z, Dimitrov, Latchezar M, Stanwyck, Lynn K, Meng, Weihua, Hosseini, S Mohsen, Imamura, Minako, Nousome, Darryl, Kim, Jihye, Hai, Yang, Jia, Yucheng, Ahn, Jeeyun, Leong, Aaron, Shah, Kaanan, Park, Kyu Hyung, Guo, Xiuqing, Ipp, Eli, Taylor, Kent D, Adler, Sharon G, Sedor, John R, Freedman, Barry I, Group, DCCT EDIC Research Group Family Investigation of Nephropathy and Diabetes-Eye Research, Lee, I-Te, Sheu, Wayne H-H, Kubo, Michiaki, Takahashi, Atsushi, Hadjadj, Samy, Marre, Michel, Tregouet, David-Alexandre, Mckean-Cowdin, Roberta, Varma, Rohit, McCarthy, Mark I, Groop, Leif, Ahlqvist, Emma, Lyssenko, Valeriya, Agardh, Elisabet, Morris, Andrew, Doney, Alex SF, Colhoun, Helen M, Toppila, Iiro, Sandholm, Niina, Groop, Per-Henrik, Maeda, Shiro, Hanis, Craig L, Penman, Alan, Chen, Ching J, Hancock, Heather, Mitchell, Paul, Craig, Jamie E, Chew, Emily Y, Paterson, Andrew D, Grassi, Michael A, Palmer, Colin, Bowden, Donald W, Yaspan, Brian L, Siscovick, David, Cotch, Mary Frances, Wang, Jie Jin, Burdon, Kathryn P, Wong, Tien Y, Klein, Barbara EK, Klein, Ronald, Rotter, Jerome I, Iyengar, Sudha K, Price, Alkes, and Sobrin, Lucia

Subjects
Biomedical and Clinical Sciences, Genetics, Eye Disease and Disorders of Vision, Diabetes, Human Genome, Prevention, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Good Health and Well Being, Blood Glucose, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Glycated Hemoglobin, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Protein Binding, Family Investigation of Nephropathy and Diabetes-Eye Research Group, DCCT/EDIC Research Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value

Published
2019

12. A genome‐wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes

Author

Meng, Weihua, Shah, Kaanan P, Pollack, Samuela, Toppila, Iiro, Hebert, Harry L, McCarthy, Mark I, Groop, Leif, Ahlqvist, Emma, Lyssenko, Valeriya, Agardh, Elisabet, Daniell, Mark, Kaidonis, Georgia, Craig, Jamie E, Mitchell, Paul, Liew, Gerald, Kifley, Annette, Wang, Jie Jin, Christiansen, Mark W, Jensen, Richard A, Penman, Alan, Hancock, Heather A, Chen, Ching J, Correa, Adolfo, Kuo, Jane Z, Li, Xiaohui, Chen, Yii‐der I, Rotter, Jerome I, Klein, Ronald, Klein, Barbara, Wong, Tien Y, Morris, Andrew D, Doney, Alexander SF, Colhoun, Helen M, Price, Alkes L, Burdon, Kathryn P, Groop, Per‐Henrik, Sandholm, Niina, Grassi, Michael A, Sobrin, Lucia, Palmer, Colin NA, and Consortium, Surrogate markers for Micro‐and Macro‐vascular hard endpoints for Innovative diabetes Tools study group Wellcome Trust Case Control

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Genetics, Diabetes, Eye, Metabolic and endocrine, Adult, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, Humans, Laser Coagulation, Male, Middle Aged, NADPH Oxidase 4, Polymorphism, Single Nucleotide, Scotland, White People, diabetes, diabetic complications, diabetic retinopathy, genome-wide association study, NOX4, Wellcome Trust Case Control Consortium 2 (WTCCC2), Surrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) study group, Clinical Sciences, Neurosciences, Opthalmology and Optometry, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

PurposeDiabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy.MethodsA genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta-analysis using multiple Caucasian cohorts.ResultsFive hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 × 10-9 . Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values = 7.41 × 10-8 and 1.23 × 10-8 , respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p = 0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p = 0.429).ConclusionThis genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.

Published
2018

13. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

Author

Mahajan, Anubha, Wessel, Jennifer, Willems, Sara M, Zhao, Wei, Robertson, Neil R, Chu, Audrey Y, Gan, Wei, Kitajima, Hidetoshi, Taliun, Daniel, Rayner, N William, Guo, Xiuqing, Lu, Yingchang, Li, Man, Jensen, Richard A, Hu, Yao, Huo, Shaofeng, Lohman, Kurt K, Zhang, Weihua, Cook, James P, Prins, Bram Peter, Flannick, Jason, Grarup, Niels, Trubetskoy, Vassily Vladimirovich, Kravic, Jasmina, Kim, Young Jin, Rybin, Denis V, Yaghootkar, Hanieh, Müller-Nurasyid, Martina, Meidtner, Karina, Li-Gao, Ruifang, Varga, Tibor V, Marten, Jonathan, Li, Jin, Smith, Albert Vernon, An, Ping, Ligthart, Symen, Gustafsson, Stefan, Malerba, Giovanni, Demirkan, Ayse, Tajes, Juan Fernandez, Steinthorsdottir, Valgerdur, Wuttke, Matthias, Lecoeur, Cécile, Preuss, Michael, Bielak, Lawrence F, Graff, Marielisa, Highland, Heather M, Justice, Anne E, Liu, Dajiang J, Marouli, Eirini, Peloso, Gina Marie, Warren, Helen R, ExomeBP Consortium, MAGIC Consortium, GIANT Consortium, Afaq, Saima, Afzal, Shoaib, Ahlqvist, Emma, Almgren, Peter, Amin, Najaf, Bang, Lia B, Bertoni, Alain G, Bombieri, Cristina, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A, Burtt, Noël P, Canouil, Mickaël, Chen, Yii-Der Ida, Cho, Yoon Shin, Christensen, Cramer, Eastwood, Sophie V, Eckardt, Kai-Uwe, Fischer, Krista, Gambaro, Giovanni, Giedraitis, Vilmantas, Grove, Megan L, de Haan, Hugoline G, Hackinger, Sophie, Hai, Yang, Han, Sohee, Tybjærg-Hansen, Anne, Hivert, Marie-France, Isomaa, Bo, Jäger, Susanne, Jørgensen, Marit E, Jørgensen, Torben, Käräjämäki, Annemari, Kim, Bong-Jo, Kim, Sung Soo, Koistinen, Heikki A, Kovacs, Peter, Kriebel, Jennifer, Kronenberg, Florian, Läll, Kristi, Lange, Leslie A, Lee, Jung-Jin, Lehne, Benjamin, Li, Huaixing, and Lin, Keng-Hung

Subjects
ExomeBP Consortium, MAGIC Consortium, GIANT Consortium, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Chromosome Mapping, Alleles, European Continental Ancestry Group, Female, Male, Genetic Variation, Genome-Wide Association Study, Whole Exome Sequencing, Diabetes Mellitus, Type 2, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P

Published
2018

15. Replace: a randomized controlled trial on the effect of hydrocortisone or placebo in patients with reported symptoms of glucocorticoid-induced adrenal insufficiency after terminating prednisolone for polymyalgia rheumatic/giant cell arteritis

Author

Fenger, Dreyer Anja, primary, Willemoes, Borresen Stina, additional, Boggild, Hansen Simon, additional, Al-Jorani, Hajir, additional, Sofie, Bislev Lise, additional, Brun, Boesen Victor, additional, Lehmann, Christensen Louise, additional, Glintborg, Dorte, additional, Christian, Jensen Richard, additional, Thurmann, Jorgensen Nanna, additional, Klose, Marianne, additional, Louise, Lund Marie, additional, Stankovic, Jelena, additional, Tei, Randi, additional, Feldt-Rasmussen, Ulla, additional, Otto, Jorgensen Jens, additional, and Andersen, Marianne, additional

Published
2024
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16. Musculoskeletal health and body composition in patients discontinuing long-term prednisolone treatment - prospective data from the replace Study

Author

Bislev, Lise Sofie, primary, Lund, Marie Louise, additional, Dreyer, Anja Fenger, additional, Al-Jorani, Hajir, additional, Boesen, Victor Brun, additional, Borresen, Stina Willemoes, additional, Christensen, Louise Lehmann, additional, Feldt-Rasmussen, Ulla, additional, Glintborg, Dorte, additional, Hansen, Simon Boggild, additional, Jensen, Richard Christian, additional, Jorgensen, Nanna Thurmann, additional, Stankovic, Jelena, additional, Tei, Randi, additional, Andersen, Marianne Skovsager, additional, Klose, Marianne, additional, and Jorgensen, Jens OttoLunde, additional

Published
2024
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17. Impact of glucocorticoid-induced adrenal insufficiency on health-related quality of life in patients receiving long-term low dose prednisolone treatment: Results from the double edge-rescue trial

Author

Lund, Marie Louise, primary, Al-Jorani, Hajir, additional, Stankovic, Jelena, additional, Bislev, Lise Sofie, additional, Bjorner, Jakob Bue, additional, Boesen, Victor Brun, additional, Christensen, Louise Lehmann, additional, Feldt-Rasmussen, Ulla, additional, Dreyer, Anja Fenger, additional, Glintborg, Dorte, additional, Hansen, Annette, additional, Hansen, Simon Boggild, additional, Jensen, Richard Christian, additional, Jorgensen, Nanna Thurmann, additional, Klose, Marianne, additional, Locht, Henning, additional, Tei, Randi, additional, Watt, Torquil, additional, Stewart, Paul M., additional, Sorensen, Henrik Toft, additional, Jorgensen, Jens Otto, additional, Andersen, Marianne, additional, and Borresen, Stina Willemoes, additional

Published
2024
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18. Physical activity after planned cessation of prednisolone treatment in patients with polymyalgia rheumatica and/or giant cell arteritis: baseline data from the double edge-replace study

Author

Stankovic, Jelena, primary, Lund, MarieLouise, additional, Dreyer, AnjaFenger, additional, Al-Jorani, Hajir, additional, Boesen, Victor Brun, additional, Borresen, StinaWillemoes, additional, Christensen, LouiseLehmann, additional, Feldt-Rasmussen, Ulla, additional, Glintborg, Dorte, additional, Hansen, Simon Boggild, additional, Jensen, Richard Christian, additional, Jorgensen, NannaThurmann, additional, Bislev, LiseSofie, additional, Tei, Randi, additional, Andersen, Marianne, additional, and Jorgensen, JensOtto, additional

Published
2024
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19. Assessment of adrenal function after prednisolone treatment in patients with polymyalgia rheumatica and/or giant cell arteritis - Data from the double edge-replace study

Author

Boggild, Hansen Simon, primary, Fenger, Dreyer Anja, additional, Jorgensen, Nanna Thurmann, additional, Al-Jorani, Hajir, additional, Sofie, Bislev Lise, additional, Boesen, Victor Brun, additional, Borresen, Stina Willemoes, additional, Christensen, Louise Lehmann, additional, Glintborg, Dorte, additional, Hamge, Ellen, additional, Hetland, Merete Lund, additional, Jensen, Richard Christian, additional, Just, Soren Andreas, additional, Keller, Kresten, additional, Klose, Marianne, additional, Lamgesen, Kristina, additional, Lund, Marie Louise, additional, Stankovic, Jelena, additional, Stewart, Paul M, additional, Sorensen, Henrik Toft, additional, Tei, Randi, additional, Voss, Anne, additional, Feldt-Rasmussen, Ulla, additional, Jorgensen, Jens Otto, additional, and Andersen, Marianne, additional

Published
2024
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21. Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study

Author

Sobrin, Lucia, Chong, Yong He, Fan, Qiao, Gan, Alfred, Stanwyck, Lynn K, Kaidonis, Georgia, Craig, Jamie E, Kim, Jihye, Liao, Wen-Ling, Huang, Yu-Chuen, Lee, Wen-Jane, Hung, Yi-Jen, Guo, Xiuqing, Hai, Yang, Ipp, Eli, Pollack, Samuela, Hancock, Heather, Price, Alkes, Penman, Alan, Mitchell, Paul, Liew, Gerald, Smith, Albert V, Gudnason, Vilmundur, Tan, Gavin, Klein, Barbara EK, Kuo, Jane, Li, Xiaohui, Christiansen, Mark W, Psaty, Bruce M, Sandow, Kevin, Jensen, Richard A, Klein, Ronald, Cotch, Mary Frances, Wang, Jie Jin, Jia, Yucheng, Chen, Ching J, Chen, Yii-Der Ida, Rotter, Jerome I, Tsai, Fuu-Jen, Hanis, Craig L, Burdon, Kathryn P, Wong, Tien Yin, Cheng, Ching-Yu, Spracklen, Cassandra N, Chen, Peng, Kim, Young Jin, Wang, Xu, Cai, Hui, Li, Shengxu, Long, Jirong, Wu, Ying, Wang, Ya-Xing, Takeuchi, Fumihiko, Wu, Jer-Yuarn, Jung, Keum-Ji, Hu, Cheng, Akiyama, Koichi, Zhang, Yonghong, Moon, Sanghoon, Johnson, Todd A, Li, Huaixing, Dorajoo, Rajkumar, He, Meian, Cannon, Maren E, Roman, Tamara S, Salfati, Elias, Lin, Keng-Hung, Sheu, Wayne HH, Absher, Devin, Adair, Linda S, Assimes, Themistocles L, Aung, Tin, Cai, Qiuyin, Chang, Li-Ching, Chen, Chien-Hsiun, Chien, Li-Hsin, Chuang, Lee-Ming, Chuang, Shu-Chun, Du, Shufa, Fann, Cathy SJ, Feranil, Alan B, Friedlander, Yechiel, Gordon-Larsen, Penny, Gu, Dongfeng, Gui, Lixuan, Guo, Zhirong, Heng, Chew-Kiat, Hixson, James, Hou, Xuhong, Hsiung, Chao Agnes, Hu, Yao, Hwang, Mi Yeong, Hwu, Chii-Min, Isono, Masato, Juang, Jyh-Ming Jimmy, Khor, Chiea-Chuen, Kim, Yun Kyoung, Koh, Woon-Puay, Kubo, Michiaki, and Lee, I-Te

Subjects
Biomedical and Clinical Sciences, Cancer, Prevention, Eye Disease and Disorders of Vision, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Aged, Diabetic Retinopathy, Female, Genome-Wide Association Study, Humans, Lipids, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk, Asian Genetic Epidemiology Network Consortium, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.

Published
2017

22. Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium

Author

Jensen, Majken K, Jensen, Richard A, Mukamal, Kenneth J, Guo, Xiuqing, Yao, Jie, Sun, Qi, Cornelis, Marilyn, Liu, Yongmei, Chen, Ming-Huei, Kizer, Jorge R, Djoussé, Luc, Siscovick, David S, Psaty, Bruce M, Zmuda, Joseph M, Rotter, Jerome I, Garcia, Melissa, Harris, Tamara, Chen, Ida, Goodarzi, Mark O, Nalls, Michael A, Keller, Margaux, Arnold, Alice M, Newman, Anne B, Hoogeveen, Ron C, Rexrode, Kathryn M, Rimm, Eric B, Hu, Frank B, Ramachandran, Vasan S, Katz, Ronit, Pankow, James S, and Ix, Joachim H

Subjects
Human Genome, Genetics, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adult, Black or African American, Aged, Diabetes Mellitus, Type 2, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Male, Metabolic Syndrome, Middle Aged, Polymorphism, Single Nucleotide, White People, alpha-2-HS-Glycoprotein, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Plasma fetuin-A is associated with type 2 diabetes, and AHSG, the gene encoding fetuin-A, has been identified as a susceptibility locus for diabetes and metabolic syndrome. Thus far, unbiased investigations of the genetic determinants of plasma fetuin-A concentrations have not been conducted. We searched for single nucleotide polymorphisms (SNPs) related to fetuin-A concentrations by a genome-wide association study in six population-based studies. We examined the association of fetuin-A levels with ∼ 2.5 million genotyped and imputed SNPs in 9,055 participants of European descent and 2,119 African Americans. In both ethnicities, the strongest associations were centered in a region with a high degree of LD near the AHSG locus. Among 136 genome-wide significant (P

Published
2017

23. Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Author

Rusu, Victor, Hoch, Eitan, Mercader, Josep M, Tenen, Danielle E, Gymrek, Melissa, Hartigan, Christina R, DeRan, Michael, von Grotthuss, Marcin, Fontanillas, Pierre, Spooner, Alexandra, Guzman, Gaelen, Deik, Amy A, Pierce, Kerry A, Dennis, Courtney, Clish, Clary B, Carr, Steven A, Wagner, Bridget K, Schenone, Monica, Ng, Maggie CY, Chen, Brian H, Consortium, MEDIA, Shriner, Daniel, Li, Jiang, Chen, Wei-Min, Guo, Xiuqing, Liu, Jiankang, Bielinski, Suzette J, Yanek, Lisa R, Nalls, Michael A, Comeau, Mary E, Rasmussen-Torvik, Laura J, Jensen, Richard A, Evans, Daniel S, Sun, Yan V, An, Ping, Patel, Sanjay R, Lu, Yingchang, Long, Jirong, Armstrong, Loren L, Wagenknecht, Lynne, Yang, Lingyao, Snively, Beverly M, Palmer, Nicholette D, Mudgal, Poorva, Langefeld, Carl D, Keene, Keith L, Freedman, Barry I, Mychaleckyj, Josyf C, Nayak, Uma, Raffel, Leslie J, Goodarzi, Mark O, Chen, Y-D Ida, Taylor, Herman A, Correa, Adolfo, Sims, Mario, Couper, David, Pankow, James S, Boerwinkle, Eric, Adeyemo, Adebowale, Doumatey, Ayo, Chen, Guanjie, Mathias, Rasika A, Vaidya, Dhananjay, Singleton, Andrew B, Zonderman, Alan B, Igo, Robert P, Sedor, John R, Consortium, the FIND, Kabagambe, Edmond K, Siscovick, David S, McKnight, Barbara, Rice, Kenneth, Liu, Yongmei, Hsueh, Wen-Chi, Zhao, Wei, Bielak, Lawrence F, Kraja, Aldi, Province, Michael A, Bottinger, Erwin P, Gottesman, Omri, Cai, Qiuyin, Zheng, Wei, Blot, William J, Lowe, William L, Pacheco, Jennifer A, Crawford, Dana C, Consortium, the eMERGE, Consortium, the DIAGRAM, Grundberg, Elin, Consortium, the MuTHER, Rich, Stephen S, Hayes, M Geoffrey, Shu, Xiao-Ou, Loos, Ruth JF, Borecki, Ingrid B, Peyser, Patricia A, Cummings, Steven R, and Psaty, Bruce M

Subjects
Biological Sciences, Genetics, Clinical Research, Diabetes, Digestive Diseases, Liver Disease, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Basigin, Cell Membrane, Chromosomes, Human, Pair 17, Diabetes Mellitus, Type 2, Gene Knockdown Techniques, Haplotypes, Hepatocytes, Heterozygote, Histone Code, Humans, Liver, Models, Molecular, Monocarboxylic Acid Transporters, MEDIA Consortium, SIGMA T2D Consortium, MCT11, SLC16A11, disease mechanism, fatty acid metabolism, genetics, lipid metabolism, monocarboxylates, precision medicine, solute carrier, type 2 diabetes, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. VIDEO ABSTRACT.

Published
2017

24. Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

Author

Liang, Jingjing, Le, Thu H, Edwards, Digna R Velez, Tayo, Bamidele O, Gaulton, Kyle J, Smith, Jennifer A, Lu, Yingchang, Jensen, Richard A, Chen, Guanjie, Yanek, Lisa R, Schwander, Karen, Tajuddin, Salman M, Sofer, Tamar, Kim, Wonji, Kayima, James, McKenzie, Colin A, Fox, Ervin, Nalls, Michael A, Young, J Hunter, Sun, Yan V, Lane, Jacqueline M, Cechova, Sylvia, Zhou, Jie, Tang, Hua, Fornage, Myriam, Musani, Solomon K, Wang, Heming, Lee, Juyoung, Adeyemo, Adebowale, Dreisbach, Albert W, Forrester, Terrence, Chu, Pei-Lun, Cappola, Anne, Evans, Michele K, Morrison, Alanna C, Martin, Lisa W, Wiggins, Kerri L, Hui, Qin, Zhao, Wei, Jackson, Rebecca D, Ware, Erin B, Faul, Jessica D, Reiner, Alex P, Bray, Michael, Denny, Joshua C, Mosley, Thomas H, Palmas, Walter, Guo, Xiuqing, Papanicolaou, George J, Penman, Alan D, Polak, Joseph F, Rice, Kenneth, Taylor, Ken D, Boerwinkle, Eric, Bottinger, Erwin P, Liu, Kiang, Risch, Neil, Hunt, Steven C, Kooperberg, Charles, Zonderman, Alan B, Laurie, Cathy C, Becker, Diane M, Cai, Jianwen, Loos, Ruth JF, Psaty, Bruce M, Weir, David R, Kardia, Sharon LR, Arnett, Donna K, Won, Sungho, Edwards, Todd L, Redline, Susan, Cooper, Richard S, Rao, DC, Rotter, Jerome I, Rotimi, Charles, Levy, Daniel, Chakravarti, Aravinda, Zhu, Xiaofeng, and Franceschini, Nora

Subjects
Animals, Humans, Mice, Hypertension, Cadherins, Membrane Proteins, Case-Control Studies, Blood Pressure, Multifactorial Inheritance, Polymorphism, Single Nucleotide, African Americans, Female, Male, Basic Helix-Loop-Helix Transcription Factors, Genome-Wide Association Study, Genetic Loci, Kidney Disease, Cardiovascular, Human Genome, Genetics, Biotechnology, Clinical Research, 2.1 Biological and endogenous factors, Developmental Biology
Abstract

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

Published
2017

28. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

Author

Walford, Geoffrey A, Gustafsson, Stefan, Rybin, Denis, Stančáková, Alena, Chen, Han, Liu, Ching-Ti, Hong, Jaeyoung, Jensen, Richard A, Rice, Ken, Morris, Andrew P, Mägi, Reedik, Tönjes, Anke, Prokopenko, Inga, Kleber, Marcus E, Delgado, Graciela, Silbernagel, Günther, Jackson, Anne U, Appel, Emil V, Grarup, Niels, Lewis, Joshua P, Montasser, May E, Landenvall, Claes, Staiger, Harald, Luan, Jian’an, Frayling, Timothy M, Weedon, Michael N, Xie, Weijia, Morcillo, Sonsoles, Martínez-Larrad, María Teresa, Biggs, Mary L, Chen, Yii-Der Ida, Corbaton-Anchuelo, Arturo, Færch, Kristine, Gómez-Zumaquero, Juan Miguel, Goodarzi, Mark O, Kizer, Jorge R, Koistinen, Heikki A, Leong, Aaron, Lind, Lars, Lindgren, Cecilia, Machicao, Fausto, Manning, Alisa K, Martín-Núñez, Gracia María, Rojo-Martínez, Gemma, Rotter, Jerome I, Siscovick, David S, Zmuda, Joseph M, Zhang, Zhongyang, Serrano-Rios, Manuel, Smith, Ulf, Soriguer, Federico, Hansen, Torben, Jørgensen, Torben J, Linnenberg, Allan, Pedersen, Oluf, Walker, Mark, Langenberg, Claudia, Scott, Robert A, Wareham, Nicholas J, Fritsche, Andreas, Häring, Hans-Ulrich, Stefan, Norbert, Groop, Leif, O’Connell, Jeff R, Boehnke, Michael, Bergman, Richard N, Collins, Francis S, Mohlke, Karen L, Tuomilehto, Jaakko, März, Winfried, Kovacs, Peter, Stumvoll, Michael, Psaty, Bruce M, Kuusisto, Johanna, Laakso, Markku, Meigs, James B, Dupuis, Josée, Ingelsson, Erik, and Florez, Jose C

Subjects
Biomedical and Clinical Sciences, Genetics, Prevention, Human Genome, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Chemokines, CC, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Insulin Receptor Substrate Proteins, Insulin Resistance, Male, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-bcl-2, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.

Published
2016

29. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Author

Liu, Ching-Ti, Raghavan, Sridharan, Maruthur, Nisa, Kabagambe, Edmond Kato, Hong, Jaeyoung, Ng, Maggie CY, Hivert, Marie-France, Lu, Yingchang, An, Ping, Bentley, Amy R, Drolet, Anne M, Gaulton, Kyle J, Guo, Xiuqing, Armstrong, Loren L, Irvin, Marguerite R, Li, Man, Lipovich, Leonard, Rybin, Denis V, Taylor, Kent D, Agyemang, Charles, Palmer, Nicholette D, Cade, Brian E, Chen, Wei-Min, Dauriz, Marco, Delaney, Joseph AC, Edwards, Todd L, Evans, Daniel S, Evans, Michele K, Lange, Leslie A, Leong, Aaron, Liu, Jingmin, Liu, Yongmei, Nayak, Uma, Patel, Sanjay R, Porneala, Bianca C, Rasmussen-Torvik, Laura J, Snijder, Marieke B, Stallings, Sarah C, Tanaka, Toshiko, Yanek, Lisa R, Zhao, Wei, Becker, Diane M, Bielak, Lawrence F, Biggs, Mary L, Bottinger, Erwin P, Bowden, Donald W, Chen, Guanjie, Correa, Adolfo, Couper, David J, Crawford, Dana C, Cushman, Mary, Eicher, John D, Fornage, Myriam, Franceschini, Nora, Fu, Yi-Ping, Goodarzi, Mark O, Gottesman, Omri, Hara, Kazuo, Harris, Tamara B, Jensen, Richard A, Johnson, Andrew D, Jhun, Min A, Karter, Andrew J, Keller, Margaux F, Kho, Abel N, Kizer, Jorge R, Krauss, Ronald M, Langefeld, Carl D, Li, Xiaohui, Liang, Jingling, Liu, Simin, Lowe, William L, Mosley, Thomas H, North, Kari E, Pacheco, Jennifer A, Peyser, Patricia A, Patrick, Alan L, Rice, Kenneth M, Selvin, Elizabeth, Sims, Mario, Smith, Jennifer A, Tajuddin, Salman M, Vaidya, Dhananjay, Wren, Mary P, Yao, Jie, Zhu, Xiaofeng, Ziegler, Julie T, Zmuda, Joseph M, Zonderman, Alan B, Zwinderman, Aeilko H, Consortium, AAAG, Consortium, CARe, Consortium, COGENT-BP, Consortium, eMERGE, Consortium, MEDIA, Adeyemo, Adebowale, Boerwinkle, Eric, Ferrucci, Luigi, Hayes, M Geoffrey, and Kardia, Sharon LR

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Health Disparities, Human Genome, Diabetes, Minority Health, Metabolic and endocrine, Asian People, Black People, Blood Glucose, Diabetes Mellitus, Type 2, Enhancer Elements, Genetic, Ethnicity, Fasting, Female, Gene Frequency, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Introns, Islets of Langerhans, Male, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Transcription Factors, White People, AAAG Consortium, CARe Consortium, COGENT-BP Consortium, eMERGE Consortium, MEDIA Consortium, MAGIC Consortium, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

Published
2016

30. General Framework for Meta‐Analysis of Haplotype Association Tests

Author

Wang, Shuai, Zhao, Jing Hua, An, Ping, Guo, Xiuqing, Jensen, Richard A, Marten, Jonathan, Huffman, Jennifer E, Meidtner, Karina, Boeing, Heiner, Campbell, Archie, Rice, Kenneth M, Scott, Robert A, Yao, Jie, Schulze, Matthias B, Wareham, Nicholas J, Borecki, Ingrid B, Province, Michael A, Rotter, Jerome I, Hayward, Caroline, Goodarzi, Mark O, Meigs, James B, and Dupuis, Josée

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Aging, Human Genome, Co-Repressor Proteins, Cohort Studies, DNA-Binding Proteins, Fasting, Female, Genetic Association Studies, Genetic Variation, Glucose, Glucose-6-Phosphatase, Haplotypes, Heart, Humans, Least-Squares Analysis, Male, Meta-Analysis as Topic, Models, Genetic, Molecular Epidemiology, Multivariate Analysis, Neoplasm Proteins, Phenotype, Reproducibility of Results, Research Design, meta-analysis, haplotype association tests, family samples, linear mixed effects model, Public Health and Health Services
Abstract

For complex traits, most associated single nucleotide variants (SNV) discovered to date have a small effect, and detection of association is only possible with large sample sizes. Because of patient confidentiality concerns, it is often not possible to pool genetic data from multiple cohorts, and meta-analysis has emerged as the method of choice to combine results from multiple studies. Many meta-analysis methods are available for single SNV analyses. As new approaches allow the capture of low frequency and rare genetic variation, it is of interest to jointly consider multiple variants to improve power. However, for the analysis of haplotypes formed by multiple SNVs, meta-analysis remains a challenge, because different haplotypes may be observed across studies. We propose a two-stage meta-analysis approach to combine haplotype analysis results. In the first stage, each cohort estimate haplotype effect sizes in a regression framework, accounting for relatedness among observations if appropriate. For the second stage, we use a multivariate generalized least square meta-analysis approach to combine haplotype effect estimates from multiple cohorts. Haplotype-specific association tests and a global test of independence between haplotypes and traits are obtained within our framework. We demonstrate through simulation studies that we control the type-I error rate, and our approach is more powerful than inverse variance weighted meta-analysis of single SNV analysis when haplotype effects are present. We replicate a published haplotype association between fasting glucose-associated locus (G6PC2) and fasting glucose in seven studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and we provide more precise haplotype effect estimates.

Published
2016

31. Novel Genetic Loci Associated With Retinal Microvascular Diameter

Author

Jensen, Richard A, Sim, Xueling, Smith, Albert Vernon, Li, Xiaohui, Jakobsdóttir, Jóhanna, Cheng, Ching-Yu, Brody, Jennifer A, Cotch, Mary Frances, Mcknight, Barbara, Klein, Ronald, Wang, Jie Jin, Kifley, Annette, Harris, Tamara B, Launer, Lenore J, Taylor, Kent D, Klein, Barbara EK, Raffel, Leslie J, Li, Xiang, Ikram, M Arfan, Klaver, Caroline C, van der Lee, Sven J, Mutlu, Unal, Hofman, Albert, Uitterlinden, André G, Liu, Chunyu, Kraja, Aldi T, Mitchell, Paul, Gudnason, Vilmundur, Rotter, Jerome I, Boerwinkle, Eric, van Duijn, Cornelia M, Psaty, Bruce M, and Wong, Tien Y

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Eye Disease and Disorders of Vision, Clinical Research, Human Genome, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Adult, Aged, Aged, 80 and over, Alleles, Arterioles, DNA-Binding Proteins, Female, Gene Frequency, Genetic Loci, Humans, Male, Middle Aged, Nuclear Proteins, Polymorphism, Single Nucleotide, Retinal Artery, Retinal Vein, TEA Domain Transcription Factors, Tetraspanins, Transcription Factors, Venules, meta-analysis, genetics, microcirculation, exome, retina, CHARGE Exome Chip Blood Pressure Consortium, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundThere is increasing evidence that retinal microvascular diameters are associated with cardiovascular and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size.Methods and resultsThis study extends previous genome-wide association study results using 24 000+ multiethnic participants from 7 discovery cohorts and 5000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single-nucleotide polymorphisms and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent and the central retinal arteriole equivalent. We report 4 new loci associated with central retinal venule equivalent, one of which is also associated with central retinal arteriole equivalent. The 4 single-nucleotide polymorphisms are rs7926971 in TEAD1 (P=3.1×10(-) (11); minor allele frequency=0.43), rs201259422 in TSPAN10 (P=4.4×10(-9); minor allele frequency=0.27), rs5442 in GNB3 (P=7.0×10(-10); minor allele frequency=0.05), and rs1800407 in OCA2 (P=3.4×10(-8); minor allele frequency=0.05). The latter single-nucleotide polymorphism, rs1800407, was also associated with central retinal arteriole equivalent (P=6.5×10(-12)). Results from the gene-based burden tests were null. In phenotype look-ups, single-nucleotide polymorphism rs201255422 was associated with both systolic (P=0.001) and diastolic blood pressures (P=8.3×10(-04)).ConclusionsOur study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease.

Published
2016

32. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.

Author

Wessel, Jennifer, Chu, Audrey Y, Willems, Sara M, Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A, Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E, An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J, Grarup, Niels, Ehm, Margaret G, Li, Li, Baldridge, Abigail S, Stančáková, Alena, Abrol, Ravinder, Besse, Céline, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F, Garcia, Melissa E, Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A, Layton, Jill C, Li, Man, Hua Zhao, Jing, Meidtner, Karina, Morrison, Alanna C, Nalls, Mike A, Peters, Marjolein J, Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V, Southam, Lorraine, Stoiber, Marcus H, Strawbridge, Rona J, Taylor, Kent D, Varga, Tibor V, Allin, Kristine H, Amin, Najaf, Aponte, Jennifer L, Aung, Tin, Barbieri, Caterina, Bihlmeyer, Nathan A, Boehnke, Michael, Bombieri, Cristina, Bowden, Donald W, Burns, Sean M, Chen, Yuning, Chen, Yii-DerI, Cheng, Ching-Yu, Correa, Adolfo, Czajkowski, Jacek, Dehghan, Abbas, Ehret, Georg B, Eiriksdottir, Gudny, Escher, Stefan A, Farmaki, Aliki-Eleni, Frånberg, Mattias, Gambaro, Giovanni, Giulianini, Franco, Goddard, William A, Goel, Anuj, Gottesman, Omri, Grove, Megan L, Gustafsson, Stefan, Hai, Yang, Hallmans, Göran, Heo, Jiyoung, Hoffmann, Per, Ikram, Mohammad K, Jensen, Richard A, Jørgensen, Marit E, Jørgensen, Torben, Karaleftheri, Maria, Khor, Chiea C, Kirkpatrick, Andrea, Kraja, Aldi T, Kuusisto, Johanna, Lange, Ethan M, Lee, IT, Lee, Wen-Jane, Leong, Aaron, Liao, Jiemin, Liu, Chunyu, Liu, Yongmei, Lindgren, Cecilia M, Linneberg, Allan, and Malerba, Giovanni

Subjects
EPIC-InterAct Consortium, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Insulin, Glucose-6-Phosphatase, Blood Glucose, Oligonucleotide Array Sequence Analysis, Fasting, Polymorphism, Single Nucleotide, African Continental Ancestry Group, European Continental Ancestry Group, Genetic Variation, Genetic Loci, Genetic Association Studies, Mutation Rate, Exome, Glucagon-Like Peptide-1 Receptor, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, Diabetes, Genetics, Nutrition, Clinical Research, Prevention, Human Genome, 2.1 Biological and endogenous factors, Metabolic and Endocrine
Abstract

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

Published
2015

36. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

Author

Ng, Maggie CY, Shriner, Daniel, Chen, Brian H, Li, Jiang, Chen, Wei-Min, Guo, Xiuqing, Liu, Jiankang, Bielinski, Suzette J, Yanek, Lisa R, Nalls, Michael A, Comeau, Mary E, Rasmussen-Torvik, Laura J, Jensen, Richard A, Evans, Daniel S, Sun, Yan V, An, Ping, Patel, Sanjay R, Lu, Yingchang, Long, Jirong, Armstrong, Loren L, Wagenknecht, Lynne, Yang, Lingyao, Snively, Beverly M, Palmer, Nicholette D, Mudgal, Poorva, Langefeld, Carl D, Keene, Keith L, Freedman, Barry I, Mychaleckyj, Josyf C, Nayak, Uma, Raffel, Leslie J, Goodarzi, Mark O, Chen, Y-D Ida, Taylor, Herman A, Correa, Adolfo, Sims, Mario, Couper, David, Pankow, James S, Boerwinkle, Eric, Adeyemo, Adebowale, Doumatey, Ayo, Chen, Guanjie, Mathias, Rasika A, Vaidya, Dhananjay, Singleton, Andrew B, Zonderman, Alan B, Igo, Robert P, Sedor, John R, FIND Consortium, Kabagambe, Edmond K, Siscovick, David S, McKnight, Barbara, Rice, Kenneth, Liu, Yongmei, Hsueh, Wen-Chi, Zhao, Wei, Bielak, Lawrence F, Kraja, Aldi, Province, Michael A, Bottinger, Erwin P, Gottesman, Omri, Cai, Qiuyin, Zheng, Wei, Blot, William J, Lowe, William L, Pacheco, Jennifer A, Crawford, Dana C, eMERGE Consortium, DIAGRAM Consortium, Grundberg, Elin, MuTHER Consortium, Rich, Stephen S, Hayes, M Geoffrey, Shu, Xiao-Ou, Loos, Ruth JF, Borecki, Ingrid B, Peyser, Patricia A, Cummings, Steven R, Psaty, Bruce M, Fornage, Myriam, Iyengar, Sudha K, Evans, Michele K, Becker, Diane M, Kao, WH Linda, Wilson, James G, Rotter, Jerome I, Sale, Michèle M, Liu, Simin, Rotimi, Charles N, Bowden, Donald W, and MEta-analysis of type 2 DIabetes in African Americans Consortium

Subjects
FIND Consortium, eMERGE Consortium, DIAGRAM Consortium, MuTHER Consortium, MEta-analysis of type 2 DIabetes in African Americans Consortium, Humans, Diabetes Mellitus, Type 2, HMGA2 Protein, HLA-B27 Antigen, Polymorphism, Single Nucleotide, African Americans, Mutant Chimeric Proteins, KCNQ1 Potassium Channel, Genome-Wide Association Study, Transcription Factor 7-Like 2 Protein, Human Genome, Diabetes, Genetics, 2.1 Biological and endogenous factors, Metabolic and endocrine, Developmental Biology
Abstract

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)

Published
2014

38. Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Author

Medici, Marco, Porcu, Eleonora, Pistis, Giorgio, Teumer, Alexander, Brown, Suzanne J, Jensen, Richard A, Rawal, Rajesh, Roef, Greet L, Plantinga, Theo S, Vermeulen, Sita H, Lahti, Jari, Simmonds, Matthew J, Husemoen, Lise Lotte N, Freathy, Rachel M, Shields, Beverley M, Pietzner, Diana, Nagy, Rebecca, Broer, Linda, Chaker, Layal, Korevaar, Tim IM, Plia, Maria Grazia, Sala, Cinzia, Völker, Uwe, Richards, J Brent, Sweep, Fred C, Gieger, Christian, Corre, Tanguy, Kajantie, Eero, Thuesen, Betina, Taes, Youri E, Visser, W Edward, Hattersley, Andrew T, Kratzsch, Jürgen, Hamilton, Alexander, Li, Wei, Homuth, Georg, Lobina, Monia, Mariotti, Stefano, Soranzo, Nicole, Cocca, Massimiliano, Nauck, Matthias, Spielhagen, Christin, Ross, Alec, Arnold, Alice, van de Bunt, Martijn, Liyanarachchi, Sandya, Heier, Margit, Grabe, Hans Jörgen, Masciullo, Corrado, Galesloot, Tessel E, Lim, Ee M, Reischl, Eva, Leedman, Peter J, Lai, Sandra, Delitala, Alessandro, Bremner, Alexandra P, Philips, David IW, Beilby, John P, Mulas, Antonella, Vocale, Matteo, Abecasis, Goncalo, Forsen, Tom, James, Alan, Widen, Elisabeth, Hui, Jennie, Prokisch, Holger, Rietzschel, Ernst E, Palotie, Aarno, Feddema, Peter, Fletcher, Stephen J, Schramm, Katharina, Rotter, Jerome I, Kluttig, Alexander, Radke, Dörte, Traglia, Michela, Surdulescu, Gabriela L, He, Huiling, Franklyn, Jayne A, Tiller, Daniel, Vaidya, Bijay, de Meyer, Tim, Jørgensen, Torben, Eriksson, Johan G, O'Leary, Peter C, Wichmann, Eric, Hermus, Ad R, Psaty, Bruce M, Ittermann, Till, Hofman, Albert, Bosi, Emanuele, Schlessinger, David, Wallaschofski, Henri, Pirastu, Nicola, Aulchenko, Yurii S, de la Chapelle, Albert, Netea-Maier, Romana T, Gough, Stephen CL, Schwabedissen, Henriette Meyer zu, Frayling, Timothy M, and Kaufman, Jean-Marc

Subjects
Biological Sciences, Genetics, Prevention, Clinical Research, Autoimmune Disease, 2.1 Biological and endogenous factors, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Metabolic and endocrine, Autoantibodies, Genetic Loci, Genome-Wide Association Study, Graves Disease, Hashimoto Disease, Humans, Iodide Peroxidase, Risk Factors, Thyroiditis, Autoimmune, Thyrotropin, Developmental Biology
Abstract

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P

Published
2014

41. Technology-Driven Planning: Principles to Practice.

Author

Society for Coll. and Univ. Planning, Ann Arbor, MI., Boettcher, Judith V., Doyle, Mary M., Jensen, Richard W., Boettcher, Judith V., Doyle, Mary M., Jensen, Richard W., and Society for Coll. and Univ. Planning, Ann Arbor, MI.

Abstract

The selections in this collection explore topics related to the future of information technology and strategic, academic, resource, and facilities planning in institutions of higher education. Part 1, "Developing the Vision: Principles, Paradigms, Life Cycles, and Values," contains: (1) "Mega-Level Strategic Planning: Beyond Conventional Wisdom" (Roger Kaufman and Dale W. Lick); (2) "Change Creation: The Rest of the Planning Story" (Dale W. Lick and Roger Kaufman); (3) "Academic Leadership Strategies: Partnerships for Change" (Gretchen M. Bataille); and (4) "Technology's Contributions to Academic Planning" (J. Thomas Bowen). Part 2, "Implementing the Vision: Principles, Strategies, and Curricula,: contains: (5) "Academic Planning and Technology" (David G. Brown); (6) "The Impact of Technology on Institutional Planning" (Ellen-Earle Chaffee); (7) "Cycles in Curriculum Planning" (John E. Kolb, Gary A. Gabriele, and Sharon Roy); and (8) "Does a College Curriculum Have a Life Cycle?" (John T. Harwood). In part 3, "Supporting the Vision: The Campus Digital Plan," the chapters are: (9) "Planning for IT in Higher Education: It's Not an Oxymoron" (John W. McCredie); (10) "Life-Cycle Costs: More Than the Cost of Hardware" (Christopher S. Peebles); and (11) "Virginia Tech Faculty Development Institute" (John F. Moore and J. Thomas Head) with "Planning Practice: The IT Staffing Puzzle" (Martin Ringle) and "Planning Practice: Community-Based Planning for Technology" (R. Dan Walleri). Part 4, "Integrating the Vision: Physical and Digital Learning Environments," contains: (12)"IT Considerations in Facilities Planning" (Joel L. Hartman); (13) "Planning for Classroom Technology" (Margaret McDermott and David E. Hollowell); and (14) "Developing and Supporting High-Technology Facilities" (Bruce M. Taggart), with "Planning Practice: From Blueprints and Spreadsheets to the Web" (Patricia Seller-Wolff and Mark Wells) and "Planning Practice: New Tools for Community College Facilities Planning" (Patricia C. Williamson). A conclusion, "Realizing the Vision: Concluding Thoughts," summarizes some of the major points. Each chapter contains references. (SLD)

Published
2000

42. SMIM1 absence is associated with reduced energy expenditure and excess weight

Author

Banasik, Karina, Bay, Jakob, Boldsen, Jens Kjærgaard, Brodersen, Thorsten, Brunak, Søren, Burgdorf, Kristoffer, Chalmer, Mona Ameri, Didriksen, Maria, Dinh, Khoa Manh, Dowsett, Joseph, Erikstrup, Christian, Feenstra, Bjarke, Geller, Frank, Gudbjartsson, Daniel, Hansen, Thomas Folkmann, Hindhede, Lotte, Hjalgrim, Henrik, Jacobsen, Rikke Louise, Jemec, Gregor, Jensen, Bitten Aagaard, Kaspersen, Katrine, Kjerulff, Bertram Dalskov, Kogelman, Lisette, Hørup Larsen, Margit Anita, Louloudis, Ioannis, Lundgaard, Agnete, Susan, Mikkelsen, Christina, Nissen, Ioanna, Nyegaard, Mette, Ostrowski, Sisse Rye, Pedersen, Ole Birger, Henriksen, Alexander Pil, Rohde, Palle Duun, Rostgaard, Klaus, Schwinn, Michael, Stefansson, Kari, Stefánsson, Hreinn, Sørensen, Erik, þorsteinsdóttir, Unnur, Thørner, Lise Wegner, Bruun, Mie Topholm, Ullum, Henrik, Werge, Thomas, Westergaard, David, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian’an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Katie Chan, Kei Hang, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Loz, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V.R., Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P., Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Southam, Lorraine, Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J.L., Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J.C., Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M. Arfan, Johnson, W. Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R.H.J., Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, Van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Goncalo R., Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Ida Chen, Yii-Der, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, Janaka de Silva, H., Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J. Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L.R., Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J.F., Magnusson, Patrik K.E., Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P. Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I.A., Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E. Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G.M., Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C.J., Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Stefanucci, Luca, Moslemi, Camous, Tomé, Ana R., Virtue, Samuel, Bidault, Guillaume, Gleadall, Nicholas S., Watson, Laura P.E., Kwa, Jing E., Burden, Frances, Farrow, Samantha, Võsa, Urmo, Burling, Keith, Walker, Lindsay, Ord, John, Barker, Peter, Warner, James, Frary, Amy, Renhstrom, Karola, Ashford, Sofie E., Piper, Jo, Biggs, Gail, Erber, Wendy N., Hoffman, Gary J., Schoenmakers, Nadia, Rieneck, Klaus, Dziegiel, Morten H., Azzu, Vian, Vacca, Michele, Aparicio, Hugo Javier, Hui, Qin, Cho, Kelly, Sun, Yan V., Wilson, Peter W., Bayraktar, Omer A., Vidal-Puig, Antonio, Ostrowski, Sisse R., Astle, William J., Olsson, Martin L., Storry, Jill R., Pedersen, Ole B., Ouwehand, Willem H., Chatterjee, Krishna, Vuckovic, Dragana, and Frontini, Mattia

Published
2024
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43. TALE OF THE TIN GOOSE

Author

Jensen, Richard

Subjects
Aircraft, Air travel -- Michigan, Aerospace and defense industries, History
Abstract

IN THE LATE 1920S, THE STURDY FORD TRI-MOTOR HELPED CONVINCE A WARY AMERICAN PUBLIC THAT COMMERCIAL AIR TRAVEL COULD BE SAFE, RELIABLE AND ECONOMICAL 'I SHOULD LIKE R THOUSAND DOLLARS, [...]

Published
2020

44. SAD SAGA OF THE KEE BIRD: WHEN A B-29 CREW GOT LOST IN WEATHER OVER THE ARCTIC AND CAME DOWN ON A FROZEN GREENLAND LAKE, IT LED TO AN ILL-FATED RECOVERY ATTEMPT 48 YEARS LATER

Author

Jensen, Richard

Subjects
Boeing Co., Weather, Aircraft industry, Strategic bombers, Polar bear, Aerospace and defense industries, History, B-29 (Aircraft)
Abstract

'WHAT ARE YOU GUYS DOING IN GREENLAND?' ASKED A RADIO OPERATOR AT LADD FIELD NEAR FAIRBANKS, ALASKA. 'We came down to shoot a few polar bears,' replied radio operator Tech. [...]

Published
2020

47. UNIVERSITY STARTUP INTENSITY AND FACULTY QUALITY

Author

Showalter, Dean and Jensen, Richard

Subjects
Venture capitalists (Persons) -- Surveys -- Analysis, Venture capital -- Analysis, Technology, Legal fees, Venture capital, Business, general, Economics, National Research Council
Abstract

Using a theoretical model of university technology transfer and licensing survey data from 1991 to 2013, we show that greater faculty quality and venture capital availability is positively associated with licenses to startups. We employ a two-stage game of licensing terms (royalty rate and fixed fee) and development efforts to show that under reasonable conditions, licensing to a startup rather than an established firm will be more attractive to a technology transfer office (TTO) because the inventor's ownership share in a startup firm will increase total development efforts by the inventor and licensee. TTOs will be more likely to target startup licensees when the marginal effect of the faculty inventor's additional development effort on the probability of success is large relative to that of the venture capitalist or established firm. Empirical evidence supports the results of the model; using Associated University Technology Data licensing survey data and employing panel and cross-sectional analyses, we show that an increase in the quality of engineering faculty has roughly twice the positive impact on startup licenses than on established firm licenses. Startup licensing is also strongly impacted by venture capital availability within institutions over time. (JEL L24, L26, D86), I. INTRODUCTION The transfer of scientific knowledge from universities to industry has increased substantially in recent years, creating real effects by spurring innovation and productivity in private firms. As a [...]

Published
2019
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48. Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

Author

Jensen, Richard A, Sim, Xueling, Li, Xiaohui, Cotch, Mary Frances, Ikram, M Kamran, Holliday, Elizabeth G, Eiriksdottir, Gudny, Harris, Tamara B, Jonasson, Fridbert, Klein, Barbara EK, Launer, Lenore J, Smith, Albert Vernon, Boerwinkle, Eric, Cheung, Ning, Hewitt, Alex W, Liew, Gerald, Mitchell, Paul, Wang, Jie Jin, Attia, John, Scott, Rodney, Glazer, Nicole L, Lumley, Thomas, McKnight, Barbara, Psaty, Bruce M, Taylor, Kent, Hofman, Albert, de Jong, Paulus TVM, Rivadeneira, Fernando, Uitterlinden, Andre G, Tay, Wan-Ting, Teo, Yik Ying, Seielstad, Mark, Liu, Jianjun, Cheng, Ching-Yu, Saw, Seang-Mei, Aung, Tin, Ganesh, Santhi K, O'Donnell, Christopher J, Nalls, Mike A, Wiggins, Kerri L, Kuo, Jane Z, team, The Blue Mountains Eye Study GWAS, Consortium, CKDGen, van Duijn, Cornelia M, Gudnason, Vilmundur, Klein, Ronald, Siscovick, David S, Rotter, Jerome I, Tai, E Shong, Vingerling, Johannes, and Wong, Tien Y

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Human Genome, Hypertension, Diabetes, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Cardiovascular, Aged, Aged, 80 and over, Female, Genome-Wide Association Study, Genotype, Histone Deacetylases, Humans, Male, Polymorphism, Single Nucleotide, Repressor Proteins, Retinal Diseases, Blue Mountains Eye Study GWAS Team, CKDGen Consortium, General Science & Technology
Abstract

BackgroundMild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.MethodsA working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.ResultsNo SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3±0.23 (beta ± standard error), p = 6.6×10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%), the quality of the imputation was moderate (r(2) ∼0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.ConclusionsThis GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

Published
2013

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