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1. A methodology for gene level omics-WAS integration identifies genes influencing traits associated with cardiovascular risks: the Long Life Family Study

Author: Acharya, Sandeep, Liao, Shu, Jung, Wooseok J., Kang, Yu S., Moghaddam, Vaha Akbary, Feitosa, Mary F., Wojczynski, Mary K., Lin, Shiow, Anema, Jason A., Schwander, Karen, Connell, Jeff O., Province, Michael A., and Brent, Michael R.
Published: 2024
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2. Highly Accurate Disease Diagnosis and Highly Reproducible Biomarker Identification with PathFormer

Author: Dong, Zehao, Zhao, Qihang, Payne, Philip R. O., Province, Michael A, Cruchaga, Carlos, Zhang, Muhan, Zhao, Tianyu, Chen, Yixin, and Li, Fuhai
Subjects: Quantitative Biology - Genomics, Computer Science - Artificial Intelligence, Computer Science - Machine Learning
Abstract: Biomarker identification is critical for precise disease diagnosis and understanding disease pathogenesis in omics data analysis, like using fold change and regression analysis. Graph neural networks (GNNs) have been the dominant deep learning model for analyzing graph-structured data. However, we found two major limitations of existing GNNs in omics data analysis, i.e., limited-prediction (diagnosis) accuracy and limited-reproducible biomarker identification capacity across multiple datasets. The root of the challenges is the unique graph structure of biological signaling pathways, which consists of a large number of targets and intensive and complex signaling interactions among these targets. To resolve these two challenges, in this study, we presented a novel GNN model architecture, named PathFormer, which systematically integrate signaling network, priori knowledge and omics data to rank biomarkers and predict disease diagnosis. In the comparison results, PathFormer outperformed existing GNN models significantly in terms of highly accurate prediction capability ( 30% accuracy improvement in disease diagnosis compared with existing GNN models) and high reproducibility of biomarker ranking across different datasets. The improvement was confirmed using two independent Alzheimer's Disease (AD) and cancer transcriptomic datasets. The PathFormer model can be directly applied to other omics data analysis studies.
Published: 2024
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3. Rethinking the Power of Graph Canonization in Graph Representation Learning with Stability

Author: Dong, Zehao, Zhang, Muhan, Payne, Philip R. O., Province, Michael A, Cruchaga, Carlos, Zhao, Tianyu, Li, Fuhai, and Chen, Yixin
Subjects: Computer Science - Machine Learning
Abstract: The expressivity of Graph Neural Networks (GNNs) has been studied broadly in recent years to reveal the design principles for more powerful GNNs. Graph canonization is known as a typical approach to distinguish non-isomorphic graphs, yet rarely adopted when developing expressive GNNs. This paper proposes to maximize the expressivity of GNNs by graph canonization, then the power of such GNNs is studies from the perspective of model stability. A stable GNN will map similar graphs to close graph representations in the vectorial space, and the stability of GNNs is critical to generalize their performance to unseen graphs. We theoretically reveal the trade-off of expressivity and stability in graph-canonization-enhanced GNNs. Then we introduce a notion of universal graph canonization as the general solution to address the trade-off and characterize a widely applicable sufficient condition to solve the universal graph canonization. A comprehensive set of experiments demonstrates the effectiveness of the proposed method. In many popular graph benchmark datasets, graph canonization successfully enhances GNNs and provides highly competitive performance, indicating the capability and great potential of proposed method in general graph representation learning. In graph datasets where the sufficient condition holds, GNNs enhanced by universal graph canonization consistently outperform GNN baselines and successfully improve the SOTA performance up to $31\%$, providing the optimal solution to numerous challenging real-world graph analytical tasks like gene network representation learning in bioinformatics.
Published: 2023

4. Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease

Author: Chen, Yanhua, Du, Xiaomeng, Kuppa, Annapurna, Feitosa, Mary F, Bielak, Lawrence F, O’Connell, Jeffrey R, Musani, Solomon K, Guo, Xiuqing, Kahali, Bratati, Chen, Vincent L, Smith, Albert V, Ryan, Kathleen A, Eirksdottir, Gudny, Allison, Matthew A, Bowden, Donald W, Budoff, Matthew J, Carr, John Jeffrey, Chen, Yii-Der I, Taylor, Kent D, Oliveri, Antonino, Correa, Adolfo, Crudup, Breland F, Kardia, Sharon LR, Mosley, Thomas H, Norris, Jill M, Terry, James G, Rotter, Jerome I, Wagenknecht, Lynne E, Halligan, Brian D, Young, Kendra A, Hokanson, John E, Washko, George R, Gudnason, Vilmundur, Province, Michael A, Peyser, Patricia A, Palmer, Nicholette D, and Speliotes, Elizabeth K
Subjects: Biochemistry and Cell Biology, Genetics, Biological Sciences, Digestive Diseases, Liver Disease, Hepatitis, Chronic Liver Disease and Cirrhosis, Human Genome, Prevention, 2.1 Biological and endogenous factors, Humans, Non-alcoholic Fatty Liver Disease, Genome-Wide Association Study, Liver Cirrhosis, Acyltransferases, Phospholipases, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Liver, Protein Serine-Threonine Kinases, Intracellular Signaling Peptides and Proteins, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: Nonalcoholic fatty liver disease (NAFLD) is common and partially heritable and has no effective treatments. We carried out a genome-wide association study (GWAS) meta-analysis of imaging (n = 66,814) and diagnostic code (3,584 cases versus 621,081 controls) measured NAFLD across diverse ancestries. We identified NAFLD-associated variants at torsin family 1 member B (TOR1B), fat mass and obesity associated (FTO), cordon-bleu WH2 repeat protein like 1 (COBLL1)/growth factor receptor-bound protein 14 (GRB14), insulin receptor (INSR), sterol regulatory element-binding transcription factor 1 (SREBF1) and patatin-like phospholipase domain-containing protein 2 (PNPLA2), as well as validated NAFLD-associated variants at patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), apolipoprotein E (APOE), glucokinase regulator (GCKR), tribbles homolog 1 (TRIB1), glycerol-3-phosphate acyltransferase (GPAM), mitochondrial amidoxime-reducing component 1 (MARC1), microsomal triglyceride transfer protein large subunit (MTTP), alcohol dehydrogenase 1B (ADH1B), transmembrane channel like 4 (TMC4)/membrane-bound O-acyltransferase domain containing 7 (MBOAT7) and receptor-type tyrosine-protein phosphatase δ (PTPRD). Implicated genes highlight mitochondrial, cholesterol and de novo lipogenesis as causally contributing to NAFLD predisposition. Phenome-wide association study (PheWAS) analyses suggest at least seven subtypes of NAFLD. Individuals in the top 10% and 1% of genetic risk have a 2.5-fold to 6-fold increased risk of NAFLD, cirrhosis and hepatocellular carcinoma. These genetic variants identify subtypes of NAFLD, improve estimates of disease risk and can guide the development of targeted therapeutics.
Published: 2023

5. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Author: Suzuki, Ken, Hatzikotoulas, Konstantinos, Southam, Lorraine, Taylor, Henry J., Yin, Xianyong, Lorenz, Kim M., Mandla, Ravi, Huerta-Chagoya, Alicia, Melloni, Giorgio E. M., Kanoni, Stavroula, Rayner, Nigel W., Bocher, Ozvan, Arruda, Ana Luiza, Sonehara, Kyuto, Namba, Shinichi, Lee, Simon S. K., Preuss, Michael H., Petty, Lauren E., Schroeder, Philip, Vanderwerff, Brett, Kals, Mart, Bragg, Fiona, Lin, Kuang, Guo, Xiuqing, Zhang, Weihua, Yao, Jie, Kim, Young Jin, Graff, Mariaelisa, Takeuchi, Fumihiko, Nano, Jana, Lamri, Amel, Nakatochi, Masahiro, Moon, Sanghoon, Scott, Robert A., Cook, James P., Lee, Jung-Jin, Pan, Ian, Taliun, Daniel, Parra, Esteban J., Chai, Jin-Fang, Bielak, Lawrence F., Tabara, Yasuharu, Hai, Yang, Thorleifsson, Gudmar, Grarup, Niels, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloé, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Kwak, Soo-Heon, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Nongmaithem, Suraj S., Noordam, Raymond, Lim, Victor J. Y., Tam, Claudia H. T., Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M., Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R., Chen, Guanjie, Brody, Jennifer A., Kabagambe, Edmond, An, Ping, Xiang, Anny H., Choi, Hyeok Sun, Cade, Brian E., Tan, Jingyi, Broadaway, K. Alaine, Williamson, Alice, Kamali, Zoha, Cui, Jinrui, Thangam, Manonanthini, Adair, Linda S., Adeyemo, Adebowale, Aguilar-Salinas, Carlos A., Ahluwalia, Tarunveer S., Anand, Sonia S., Bertoni, Alain, Bork-Jensen, Jette, Brandslund, Ivan, Buchanan, Thomas A., Burant, Charles F., Butterworth, Adam S., Canouil, Mickaël, Chan, Juliana C. N., Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Cushman, Mary, Danesh, John, Das, Swapan K., de Silva, H. Janaka, Dedoussis, George, Dimitrov, Latchezar, Doumatey, Ayo P., Du, Shufa, Duan, Qing, Eckardt, Kai-Uwe, Emery, Leslie S., Evans, Daniel S., Evans, Michele K., Fischer, Krista, Floyd, James S., Ford, Ian, Franco, Oscar H., Frayling, Timothy M., Freedman, Barry I., Genter, Pauline, Gerstein, Hertzel C., Giedraitis, Vilmantas, González-Villalpando, Clicerio, González-Villalpando, Maria Elena, Gordon-Larsen, Penny, Gross, Myron, Guare, Lindsay A., Hackinger, Sophie, Hakaste, Liisa, Han, Sohee, Hattersley, Andrew T., Herder, Christian, Horikoshi, Momoko, Howard, Annie-Green, Hsueh, Willa, Huang, Mengna, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Ikram, Mohammad Arfan, Ingelsson, Martin, Islam, Md. Tariqul, Isono, Masato, Jang, Hye-Mi, Jasmine, Farzana, Jiang, Guozhi, Jonas, Jost B., Jørgensen, Torben, Kamanu, Frederick K., Kandeel, Fouad R., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kaur, Varinderpal, Kawaguchi, Takahisa, Keaton, Jacob M., Kho, Abel N., Khor, Chiea-Chuen, Kibriya, Muhammad G., Kim, Duk-Hwan, Kronenberg, Florian, Kuusisto, Johanna, Läll, Kristi, Lange, Leslie A., Lee, Kyung Min, Lee, Myung-Shik, Lee, Nanette R., Leong, Aaron, Li, Liming, Li, Yun, Li-Gao, Ruifang, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Locke, Adam E., Louie, Tin, Luan, Jian’an, Luk, Andrea O., Luo, Xi, Lv, Jun, Lynch, Julie A., Lyssenko, Valeriya, Maeda, Shiro, Mamakou, Vasiliki, Mansuri, Sohail Rafik, Matsuda, Koichi, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mo, Huan, Morris, Andrew D., Moura, Filipe A., Nadler, Jerry L., Nalls, Michael A., Nayak, Uma, Ntalla, Ioanna, Okada, Yukinori, Orozco, Lorena, Patel, Sanjay R., Patil, Snehal, Pei, Pei, Pereira, Mark A., Peters, Annette, Pirie, Fraser J., Polikowsky, Hannah G., Porneala, Bianca, Prasad, Gauri, Rasmussen-Torvik, Laura J., Reiner, Alexander P., Roden, Michael, Rohde, Rebecca, Roll, Katheryn, Sabanayagam, Charumathi, Sandow, Kevin, Sankareswaran, Alagu, Sattar, Naveed, Schönherr, Sebastian, Shahriar, Mohammad, Shen, Botong, Shi, Jinxiu, Shin, Dong Mun, Shojima, Nobuhiro, Smith, Jennifer A., So, Wing Yee, Stančáková, Alena, Steinthorsdottir, Valgerdur, Stilp, Adrienne M., Strauch, Konstantin, Taylor, Kent D., Thorand, Barbara, Thorsteinsdottir, Unnur, Tomlinson, Brian, Tran, Tam C., Tsai, Fuu-Jen, Tuomilehto, Jaakko, Tusie-Luna, Teresa, Udler, Miriam S., Valladares-Salgado, Adan, van Dam, Rob M., van Klinken, Jan B., Varma, Rohit, Wacher-Rodarte, Niels, Wheeler, Eleanor, Wickremasinghe, Ananda R., van Dijk, Ko Willems, Witte, Daniel R., Yajnik, Chittaranjan S., Yamamoto, Ken, Yamamoto, Kenichi, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Yusuf, Salim, Zawistowski, Matthew, Zhang, Liang, Zheng, Wei, Raffel, Leslie J., Igase, Michiya, Ipp, Eli, Redline, Susan, Cho, Yoon Shin, Lind, Lars, Province, Michael A., Fornage, Myriam, Hanis, Craig L., Ingelsson, Erik, Zonderman, Alan B., Psaty, Bruce M., Wang, Ya-Xing, Rotimi, Charles N., Becker, Diane M., Matsuda, Fumihiko, Liu, Yongmei, Yokota, Mitsuhiro, Kardia, Sharon L. R., Peyser, Patricia A., Pankow, James S., Engert, James C., Bonnefond, Amélie, Froguel, Philippe, Wilson, James G., Sheu, Wayne H. H., Wu, Jer-Yuarn, Hayes, M. Geoffrey, Ma, Ronald C. W., Wong, Tien-Yin, Mook-Kanamori, Dennis O., Tuomi, Tiinamaija, Chandak, Giriraj R., Collins, Francis S., Bharadwaj, Dwaipayan, Paré, Guillaume, Sale, Michèle M., Ahsan, Habibul, Motala, Ayesha A., Shu, Xiao-Ou, Park, Kyong-Soo, Jukema, J. Wouter, Cruz, Miguel, Chen, Yii-Der Ida, Rich, Stephen S., McKean-Cowdin, Roberta, Grallert, Harald, Cheng, Ching-Yu, Ghanbari, Mohsen, Tai, E-Shyong, Dupuis, Josee, Kato, Norihiro, Laakso, Markku, Köttgen, Anna, Koh, Woon-Puay, Bowden, Donald W., Palmer, Colin N. A., Kooner, Jaspal S., Kooperberg, Charles, Liu, Simin, North, Kari E., Saleheen, Danish, Hansen, Torben, Pedersen, Oluf, Wareham, Nicholas J., Lee, Juyoung, Kim, Bong-Jo, Millwood, Iona Y., Walters, Robin G., Stefansson, Kari, Ahlqvist, Emma, Goodarzi, Mark O., Mohlke, Karen L., Langenberg, Claudia, Haiman, Christopher A., Loos, Ruth J. F., Florez, Jose C., Rader, Daniel J., Ritchie, Marylyn D., Zöllner, Sebastian, Mägi, Reedik, Marston, Nicholas A., Ruff, Christian T., van Heel, David A., Finer, Sarah, Denny, Joshua C., Yamauchi, Toshimasa, Kadowaki, Takashi, Chambers, John C., Ng, Maggie C. Y., Sim, Xueling, Below, Jennifer E., Tsao, Philip S., Chang, Kyong-Mi, McCarthy, Mark I., Meigs, James B., Mahajan, Anubha, Spracklen, Cassandra N., Mercader, Josep M., Boehnke, Michael, Rotter, Jerome I., Vujkovic, Marijana, Voight, Benjamin F., Morris, Andrew P., and Zeggini, Eleftheria
Published: 2024
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6. Whole-exome sequence analysis of anthropometric traits illustrates challenges in identifying effects of rare genetic variants

Author: Young, Kristin L, Fisher, Virginia, Deng, Xuan, Brody, Jennifer A, Graff, Misa, Lim, Elise, Lin, Bridget M, Xu, Hanfei, Amin, Najaf, An, Ping, Aslibekyan, Stella, Fohner, Alison E, Hidalgo, Bertha, Lenzini, Petra, Kraaij, Robert, Medina-Gomez, Carolina, Prokić, Ivana, Rivadeneira, Fernando, Sitlani, Colleen, Tao, Ran, van Rooij, Jeroen, Zhang, Di, Broome, Jai G, Buth, Erin J, Heavner, Benjamin D, Jain, Deepti, Smith, Albert V, Barnes, Kathleen, Boorgula, Meher Preethi, Chavan, Sameer, Darbar, Dawood, De Andrade, Mariza, Guo, Xiuqing, Haessler, Jeffrey, Irvin, Marguerite R, Kalyani, Rita R, Kardia, Sharon LR, Kooperberg, Charles, Kim, Wonji, Mathias, Rasika A, McDonald, Merry-Lynn, Mitchell, Braxton D, Peyser, Patricia A, Regan, Elizabeth A, Redline, Susan, Reiner, Alexander P, Rich, Stephen S, Rotter, Jerome I, Smith, Jennifer A, Weiss, Scott, Wiggins, Kerri L, Yanek, Lisa R, Arnett, Donna, Heard-Costa, Nancy L, Leal, Suzanne, Lin, Danyu, McKnight, Barbara, Province, Michael, van Duijn, Cornelia M, North, Kari E, Cupples, L Adrienne, and Liu, Ching-Ti
Subjects: Biological Sciences, Genetics, Clinical Research, Biotechnology, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Good Health and Well Being, Humans, Genome-Wide Association Study, Exome, Body Mass Index, Quantitative Trait Loci, Anthropometry, Intercellular Signaling Peptides and Proteins, Cell Cycle Proteins, body mass index, central obesity, exome sequencing, height
Abstract: Anthropometric traits, measuring body size and shape, are highly heritable and significant clinical risk factors for cardiometabolic disorders. These traits have been extensively studied in genome-wide association studies (GWASs), with hundreds of genome-wide significant loci identified. We performed a whole-exome sequence analysis of the genetics of height, body mass index (BMI) and waist/hip ratio (WHR). We meta-analyzed single-variant and gene-based associations of whole-exome sequence variation with height, BMI, and WHR in up to 22,004 individuals, and we assessed replication of our findings in up to 16,418 individuals from 10 independent cohorts from Trans-Omics for Precision Medicine (TOPMed). We identified four trait associations with single-nucleotide variants (SNVs; two for height and two for BMI) and replicated the LECT2 gene association with height. Our expression quantitative trait locus (eQTL) analysis within previously reported GWAS loci implicated CEP63 and RFT1 as potential functional genes for known height loci. We further assessed enrichment of SNVs, which were monogenic or syndromic variants within loci associated with our three traits. This led to the significant enrichment results for height, whereas we observed no Bonferroni-corrected significance for all SNVs. With a sample size of ∼20,000 whole-exome sequences in our discovery dataset, our findings demonstrate the importance of genomic sequencing in genetic association studies, yet they also illustrate the challenges in identifying effects of rare genetic variants.
Published: 2023

7. Genetic risk accentuates dietary effects on hepatic steatosis, inflammation and fibrosis in a population-based cohort

Author: Chen, Vincent L., Du, Xiaomeng, Oliveri, Antonino, Chen, Yanhua, Kuppa, Annapurna, Halligan, Brian D., Province, Michael A., and Speliotes, Elizabeth K.
Published: 2024
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8. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author: Mason, Stefanie E, Moreta-Martinez, Rafael, Labaki, Wassim W, Strand, Matthew J, Regan, Elizabeth A, Bon, Jessica, San Jose Estepar, Ruben, Casaburi, Richard, McDonald, Merry-Lynn, Rossiter, Harry B, Make, Barry, Dransfield, Mark T, Han, MeiLan K, Young, Kendra, Curtis, Jeffrey L, Stringer, Kathleen, Kinney, Greg, Hokanson, John E, San Jose Estepar, Raul, Washko, George R, Crapo, James D, Silverman, Edwin K, Cummings, Sara, Madden, Kelley, Make, Barry J, Nabbosa, Juliet, Port, Emily, Rashdi, Serine, Stepp, Lori, Watts, Shandi, Weaver, Michael, Beaty, Terri, Bowler, Russell P, Lynch, David A, Regan, Elizabeth, Anderson, Gary, Bleecker, Eugene R, Coxson, Harvey O, Crystal, Ronald G, Hogg, James C, Province, Michael A, Rennard, Stephen I, Croxton, Thomas, Gan, Weiniu, Postow, Lisa A, Viviano, Lisa M, Costa-Davis, Corinne, Malanga, Elisha, Prieto, Delia, Tal-Singer, Ruth, Farzadegan, Homayoon, Hadji, Akila, Sathe, Leena, Baraghoshi, David, Chen, Grace, Crooks, James, Knowles, Ruthie, Pratte, Katherine, Wilson, Carla, Zelarney, Pearlanne T, Kechris, Katerina J, Leach, Sonia, Hokanson, Co-Chair John E, Austin, Erin E, Czizik, Annika, Kinney, Gregory, Li, Yisha, Lutz, Sharon M, Ragland, Margaret F, Richmond, Nicole, Young, Kendra A, Cho, Michael, Castaldi, Peter J, Glass, Kimberly, Hersh, Craig, Kim, Wonji, Liu, Yang-Yu, Hersh, Craig P, Bidinger, Jacqueline, Cho, Michael H, Conrad, Douglas, and DeMeo, Dawn L
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Nutrition, Clinical Research, Prevention, 2.1 Biological and endogenous factors, Good Health and Well Being, Body Composition, Body Mass Index, Humans, Longitudinal Studies, Lung, Pectoralis Muscles, Pulmonary Disease, Chronic Obstructive, Smokers, COPD, mortality, muscle wasting, sarcopenia, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract: BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n = 9,268) and the ECLIPSE study (n = 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1% (95% CI, 2.4%-3.7%; P < .001) in COPDGene, and 2.4% (95% CI, 0.9%-4.0%; P < .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.
Published: 2022

9. Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol.

Author: Wu, Peitao, Moon, Jee-Young, Daghlas, Iyas, Franco, Giulianini, Porneala, Bianca, Ahmadizar, Fariba, Richardson, Tom, Isaksen, Jonas, Hindy, Georgy, Yao, Jie, Sitlani, Colleen, Raffield, Laura, Yanek, Lisa, Feitosa, Mary, Cuadrat, Rafael, Qi, Qibin, Arfan Ikram, M, Ellervik, Christina, Ericson, Ulrika, Goodarzi, Mark, Brody, Jennifer, Lange, Leslie, Mercader, Josep, Vaidya, Dhananjay, An, Ping, Schulze, Matthias, Masana, Lluis, Ghanbari, Mohsen, Olesen, Morten, Cai, Jianwen, Guo, Xiuqing, Floyd, James, Jäger, Susanne, Province, Michael, Kalyani, Rita, Psaty, Bruce, Orho-Melander, Marju, Ridker, Paul, Kanters, Jørgen, Uitterlinden, Andre, Davey Smith, George, Gill, Dipender, Kaplan, Robert, Kavousi, Maryam, Raghavan, Sridharan, Chasman, Daniel, Rotter, Jerome, Meigs, James, Florez, Jose, Dupuis, Josée, Liu, Ching-Ti, and Merino, Jordi
Subjects: Cholesterol, LDL, Diabetes Mellitus, Type 2, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Obesity, Risk Factors
Abstract: OBJECTIVE: LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown. RESEARCH DESIGN AND METHODS: We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses. RESULTS: A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95% CI 1.01, 1.24]) and BMI (β = 0.07 SD units [95% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95% CI 1.01, 1.08]) with a proportion mediated of 38% of the total effect (P = 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8% (P = 0.04). CONCLUSIONS: These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.
Published: 2022

10. Allele-specific variation at APOE increases nonalcoholic fatty liver disease and obesity but decreases risk of Alzheimer’s disease and myocardial infarction

Author: Palmer, Nicholette D, Kahali, Bratati, Kuppa, Annapurna, Chen, Yanhua, Du, Xiaomeng, Feitosa, Mary F, Bielak, Lawrence F, O’Connell, Jeffrey R, Musani, Solomon K, Guo, Xiuqing, Smith, Albert V, Ryan, Kathleen A, Eirksdottir, Gudny, Allison, Matthew A, Bowden, Donald W, Budoff, Matthew J, Carr, J Jeffrey, Chen, Yii-Der I, Taylor, Kent D, Correa, Adolfo, Crudup, Breland F, Halligan, Brian, Yang, Jian, Kardia, Sharon LR, Launer, Lenore J, Fu, Yi-Ping, Mosley, Thomas H, Norris, Jill M, Terry, James G, O’Donnell, Christopher J, Rotter, Jerome I, Wagenknecht, Lynne E, Gudnason, Vilmundur, Province, Michael A, Peyser, Patricia A, and Speliotes, Elizabeth K
Subjects: Biological Sciences, Genetics, Digestive Diseases, Brain Disorders, Prevention, Aging, Chronic Liver Disease and Cirrhosis, Obesity, Neurosciences, Alzheimer's Disease, Liver Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, Human Genome, Hepatitis, Dementia, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Alanine Transaminase, Alleles, Alzheimer Disease, Apolipoproteins E, Databases, Genetic, Exome, Gene Frequency, Genome-Wide Association Study, Humans, Liver, Liver Cirrhosis, Myocardial Infarction, Non-alcoholic Fatty Liver Disease, Phenotype, Polymorphism, Single Nucleotide, Prognosis, Risk Factors, Triglycerides, Medical and Health Sciences, Genetics & Heredity
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P
Published: 2021

11. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity

Author: Yaghootkar, Hanieh, Zhang, Yiying, Spracklen, Cassandra N, Karaderi, Tugce, Huang, Lam Opal, Bradfield, Jonathan, Schurmann, Claudia, Fine, Rebecca S, Preuss, Michael H, Kutalik, Zoltan, Wittemans, Laura BL, Lu, Yingchang, Metz, Sophia, Willems, Sara M, Li-Gao, Ruifang, Grarup, Niels, Wang, Shuai, Molnos, Sophie, Sandoval-Zárate, América A, Nalls, Mike A, Lange, Leslie A, Haesser, Jeffrey, Guo, Xiuqing, Lyytikäinen, Leo-Pekka, Feitosa, Mary F, Sitlani, Colleen M, Venturini, Cristina, Mahajan, Anubha, Kacprowski, Tim, Wang, Carol A, Chasman, Daniel I, Amin, Najaf, Broer, Linda, Robertson, Neil, Young, Kristin L, Allison, Matthew, Auer, Paul L, Blüher, Matthias, Borja, Judith B, Bork-Jensen, Jette, Carrasquilla, Germán D, Christofidou, Paraskevi, Demirkan, Ayse, Doege, Claudia A, Garcia, Melissa E, Graff, Mariaelisa, Guo, Kaiying, Hakonarson, Hakon, Hong, Jaeyoung, Ida Chen, Yii-Der, Jackson, Rebecca, Jakupović, Hermina, Jousilahti, Pekka, Justice, Anne E, Kähönen, Mika, Kizer, Jorge R, Kriebel, Jennifer, LeDuc, Charles A, Li, Jin, Lind, Lars, Luan, Jian'an, Mackey, David A, Mangino, Massimo, Männistö, Satu, Martin Carli, Jayne F, Medina-Gomez, Carolina, Mook-Kanamori, Dennis O, Morris, Andrew P, de Mutsert, Renée, Nauck, Matthias, Prokic, Ivana, Pennell, Craig E, Pradhan, Arund D, Psaty, Bruce M, Raitakari, Olli T, Scott, Robert A, Skaaby, Tea, Strauch, Konstantin, Taylor, Kent D, Teumer, Alexander, Uitterlinden, Andre G, Wu, Ying, Yao, Jie, Walker, Mark, North, Kari E, Kovacs, Peter, Ikram, M Arfan, van Duijn, Cornelia M, Ridker, Paul M, Lye, Stephen, Homuth, Georg, Ingelsson, Erik, Spector, Tim D, McKnight, Barbara, Province, Michael A, Lehtimäki, Terho, Adair, Linda S, Rotter, Jerome I, Reiner, Alexander P, and Wilson, James G
Subjects: Genetics, Nutrition, Prevention, Obesity, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Metabolic and endocrine, Cardiovascular, Stroke, Cancer, Adiposity, Gene Expression Regulation, Developmental, Genetic Variation, Genotype, Humans, Leptin, Models, Molecular, Protein Conformation, Racial Groups, Medical and Health Sciences, Endocrinology & Metabolism
Abstract: Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
Published: 2020

12. Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels

Author: Wang, Zhe, Chen, Han, Bartz, Traci M, Bielak, Lawrence F, Chasman, Daniel I, Feitosa, Mary F, Franceschini, Nora, Guo, Xiuqing, Lim, Elise, Noordam, Raymond, Richard, Melissa A, Wang, Heming, Cade, Brian, Cupples, L Adrienne, de Vries, Paul S, Giulanini, Franco, Lee, Jiwon, Lemaitre, Rozenn N, Martin, Lisa W, Reiner, Alex P, Rich, Stephen S, Schreiner, Pamela J, Sidney, Stephen, Sitlani, Colleen M, Smith, Jennifer A, van Dijk, Ko Willems, Yao, Jie, Zhao, Wei, Fornage, Myriam, Kardia, Sharon LR, Kooperberg, Charles, Liu, Ching-Ti, Mook-Kanamori, Dennis O, Province, Michael A, Psaty, Bruce M, Redline, Susan, Ridker, Paul M, Rotter, Jerome I, Boerwinkle, Eric, Morrison, Alanna C, and Group, on behalf of the CHARGE Gene-Lifestyle Interactions Working
Subjects: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Substance Misuse, Human Genome, Genetics, Cardiovascular, Heart Disease, Alcoholism, Alcohol Use and Health, Aetiology, 2.1 Biological and endogenous factors, Stroke, Cancer, Oral and gastrointestinal, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Alcohol Drinking, Apolipoproteins E, Cholesterol, HDL, Female, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Humans, Lipids, Male, Middle Aged, Polymorphism, Single Nucleotide, Proprotein Convertase 9, Triglycerides, White People, Young Adult, exome, gene-environment interaction, genome-wide association study, lipids, self-report, CHARGE Gene-Lifestyle Interactions Working Group, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract: BackgroundAlcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels.MethodsIn the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered.ResultsWe discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3, and CD300LG) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered (P=6.65×10-6 for the interaction test) and replicated at nominal significance level (P=0.013) in SMC5.ConclusionsIn conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.
Published: 2020

13. Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose

Author: Wu, Peitao, Rybin, Denis, Bielak, Lawrence F, Feitosa, Mary F, Franceschini, Nora, Li, Yize, Lu, Yingchang, Marten, Jonathan, Musani, Solomon K, Noordam, Raymond, Raghavan, Sridharan, Rose, Lynda M, Schwander, Karen, Smith, Albert V, Tajuddin, Salman M, Vojinovic, Dina, Amin, Najaf, Arnett, Donna K, Bottinger, Erwin P, Demirkan, Ayse, Florez, Jose C, Ghanbari, Mohsen, Harris, Tamara B, Launer, Lenore J, Liu, Jingmin, Liu, Jun, Mook-Kanamori, Dennis O, Murray, Alison D, Nalls, Mike A, Peyser, Patricia A, Uitterlinden, André G, Voortman, Trudy, Bouchard, Claude, Chasman, Daniel, Correa, Adolfo, de Mutsert, Renée, Evans, Michele K, Gudnason, Vilmundur, Hayward, Caroline, Kao, Linda, Kardia, Sharon LR, Kooperberg, Charles, Loos, Ruth JF, Province, Michael M, Rankinen, Tuomo, Redline, Susan, Ridker, Paul M, Rotter, Jerome I, Siscovick, David, Smith, Blair H, van Duijn, Cornelia, Zonderman, Alan B, Rao, DC, Wilson, James G, Dupuis, Josée, Meigs, James B, Liu, Ching-Ti, and Vassy, Jason L
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Pharmacology and Pharmaceutical Sciences, Tobacco, Aging, Tobacco Smoke and Health, Human Genome, Nutrition, Diabetes, Clinical Research, Prevention, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Aged, Black People, Blood Glucose, Cigarette Smoking, Cohort Studies, Diabetes Mellitus, Type 2, Fasting, Feasibility Studies, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, White People, General Science & Technology
Abstract: Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p
Published: 2020

14. Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium

Author: Merino, Jordi, Dashti, Hassan S, Li, Sherly X, Sarnowski, Chloé, Justice, Anne E, Graff, Misa, Papoutsakis, Constantina, Smith, Caren E, Dedoussis, George V, Lemaitre, Rozenn N, Wojczynski, Mary K, Männistö, Satu, Ngwa, Julius S, Kho, Minjung, Ahluwalia, Tarunveer S, Pervjakova, Natalia, Houston, Denise K, Bouchard, Claude, Huang, Tao, Orho-Melander, Marju, Frazier-Wood, Alexis C, Mook-Kanamori, Dennis O, Pérusse, Louis, Pennell, Craig E, de Vries, Paul S, Voortman, Trudy, Li, Olivia, Kanoni, Stavroula, Rose, Lynda M, Lehtimäki, Terho, Zhao, Jing Hua, Feitosa, Mary F, Luan, Jian’an, McKeown, Nicola M, Smith, Jennifer A, Hansen, Torben, Eklund, Niina, Nalls, Mike A, Rankinen, Tuomo, Huang, Jinyan, Hernandez, Dena G, Schulz, Christina-Alexandra, Manichaikul, Ani, Li-Gao, Ruifang, Vohl, Marie-Claude, Wang, Carol A, van Rooij, Frank JA, Shin, Jean, Kalafati, Ioanna P, Day, Felix, Ridker, Paul M, Kähönen, Mika, Siscovick, David S, Langenberg, Claudia, Zhao, Wei, Astrup, Arne, Knekt, Paul, Garcia, Melissa, Rao, DC, Qi, Qibin, Ferrucci, Luigi, Ericson, Ulrika, Blangero, John, Hofman, Albert, Pausova, Zdenka, Mikkilä, Vera, Wareham, Nick J, Kardia, Sharon LR, Pedersen, Oluf, Jula, Antti, Curran, Joanne E, Zillikens, M Carola, Viikari, Jorma S, Forouhi, Nita G, Ordovás, José M, Lieske, John C, Rissanen, Harri, Uitterlinden, André G, Raitakari, Olli T, Kiefte-de Jong, Jessica C, Dupuis, Josée, Rotter, Jerome I, North, Kari E, Scott, Robert A, Province, Michael A, Perola, Markus, Cupples, L Adrienne, Turner, Stephen T, Sørensen, Thorkild IA, Salomaa, Veikko, Liu, Yongmei, Sung, Yun J, Qi, Lu, Bandinelli, Stefania, Rich, Stephen S, de Mutsert, Renée, Tremblay, Angelo, Oddy, Wendy H, Franco, Oscar H, and Paus, Tomas
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Obesity, Human Genome, Genetics, Prevention, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Metabolic and endocrine, Aged, Aging, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Cohort Studies, Energy Intake, Female, Fibroblast Growth Factors, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Genotype, Heart Diseases, Humans, Male, Membrane Proteins, Middle Aged, Nutrients, Polymorphism, Single Nucleotide, Receptors, Retinoic Acid, White People, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P
Published: 2019

15. The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits

Author: Abecasis, Gonçalo, Akolkar, Beena, Alexander, Benjamin R., Allred, Nicholette D., Altshuler, David, Below, Jennifer E., Bergman, Richard, Beulens, Joline W.J., Blangero, John, Boehnke, Michael, Bokvist, Krister, Bottinger, Erwin, Boughton, Andrew P., Bowden, Donald, Brosnan, M. Julia, Brown, Christopher, Bruskiewicz, Kenneth, Burtt, Noël P., Carmichael, Mary, Caulkins, Lizz, Cebola, Inês, Chambers, John, Ida Chen, Yii-Der, Cherkas, Andriy, Chu, Audrey Y., Clark, Christopher, Claussnitzer, Melina, Costanzo, Maria C., Cox, Nancy J., Hoed, Marcel den, Dong, Duc, Duby, Marc, Duggirala, Ravindranath, Dupuis, Josée, Elders, Petra J.M., Engreitz, Jesse M., Fauman, Eric, Ferrer, Jorge, Flannick, Jason, Flicek, Paul, Flickinger, Matthew, Florez, Jose C., Fox, Caroline S., Frayling, Timothy M., Frazer, Kelly A., Gaulton, Kyle J., Gilbert, Clint, Gloyn, Anna L., Green, Todd, Hanis, Craig L., Hanson, Robert, Hattersley, Andrew T., Hoang, Quy, Im, Hae Kyung, Iqbal, Sidra, Jacobs, Suzanne B.R., Jang, Dong-Keun, Jordan, Tad, Kamphaus, Tania, Karpe, Fredrik, Keane, Thomas M., Kim, Seung K., Kluge, Alexandria, Koesterer, Ryan, Kudtarkar, Parul, Lage, Kasper, Lange, Leslie A., Lazar, Mitchell, Lehman, Donna, Liu, Ching-Ti, Loos, Ruth J.F., Ma, Ronald Ching-wan, MacDonald, Patrick, Massung, Jeffrey, Maurano, Matthew T., McCarthy, Mark I., McVean, Gil, Meigs, James B., Mercader, Josep M., Miller, Melissa R., Mitchell, Braxton, Mohlke, Karen L., Morabito, Samuel, Morgan, Claire, Mullican, Shannon, Narendra, Sharvari, Ng, Maggie C.Y., Nguyen, Lynette, Palmer, Colin N.A., Parker, Stephen C.J., Parrado, Antonio, Parsa, Afshin, Pawlyk, Aaron C., Pearson, Ewan R., Plump, Andrew, Province, Michael, Quertermous, Thomas, Redline, Susan, Reilly, Dermot F., Ren, Bing, Rich, Stephen S., Richards, J. Brent, Rotter, Jerome I., Ruebenacker, Oliver, Ruetten, Hartmut, Salem, Rany M., Sander, Maike, Sanders, Michael, Sanghera, Dharambir, Scott, Laura J., Sengupta, Sebanti, Siedzik, David, Sim, Xueling, Singh, Preeti, Sladek, Robert, Small, Kerrin, Smith, Philip, Stein, Peter, Spalding, Dylan, Stringham, Heather M., Sun, Ying, Susztak, Katalin, ’t Hart, Leen M., Taliun, Daniel, Taylor, Kent, Thomas, Melissa K., Todd, Jennifer A., Udler, Miriam S., Voight, Benjamin, von Grotthuss, Marcin, Wan, Andre, Welch, Ryan P., Wholley, David, Yuksel, Kaan, Zaghloul, Norann A., Jang, Dongkeun, Moriondo, Annie, Nguyen, Trang, Smadbeck, Patrick, Brandes, MacKenzie, Dornbos, Peter, Huellas-Bruskiewicz, Kenneth C., Ji, Yue, McMahon, Aoife C., Fauman, Eric B., Kamphaus, Tania Nayak, and Abecasis, Gonçalo R.
Published: 2023
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16. A saturated map of common genetic variants associated with human height

Author: Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., and Hirschhorn, Joel N.
Published: 2022
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17. A meta-analysis of genome-wide association studies identifies multiple longevity genes.

Author: Deelen, Joris, Evans, Daniel S, Arking, Dan E, Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K, Biggs, Mary L, van der Spek, Ashley, Atzmon, Gil, Ware, Erin B, Sarnowski, Chloé, Smith, Albert V, Seppälä, Ilkka, Cordell, Heather J, Dose, Janina, Amin, Najaf, Arnold, Alice M, Ayers, Kristin L, Barzilai, Nir, Becker, Elizabeth J, Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C, Cubaynes, Sarah, Cummings, Steven R, Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D, Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B, Huisman, Martijn, Hurme, Mikko A, Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon LR, Kingston, Andrew, Kirkwood, Thomas BL, Launer, Lenore J, Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B, Nie, Chao, Nohr, Ellen A, Orwoll, Eric S, Perls, Thomas T, Province, Michael A, Psaty, Bruce M, Raitakari, Olli T, Reinders, Marcel JT, Robine, Jean-Marie, Rotter, Jerome I, Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild IA, Taylor, Kent D, Uitterlinden, André G, van der Flier, Wiesje, van der Lee, Sven J, van Duijn, Cornelia M, van Heemst, Diana, Vaupel, James W, Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P, Lunetta, Kathryn L, Slagboom, P Eline, and Murabito, Joanne M
Subjects: Humans, Heat-Shock Proteins, Longevity, Apolipoprotein E2, Apolipoprotein E4, Genome-Wide Association Study
Abstract: Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
Published: 2019

18. Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

Author: Spracklen, Cassandra N, Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S, Kutalik, Zoltan, Preuss, Michael H, Lu, Yingchang, Wittemans, Laura BL, Adair, Linda S, Allison, Matthew, Amin, Najaf, Auer, Paul L, Bartz, Traci M, Blüher, Matthias, Boehnke, Michael, Borja, Judith B, Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I, Chen, Yii-Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M, Feitosa, Mary F, Garcia, Melissa E, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B, Highland, Heather M, Hong, Jaeyoung, Ikram, M Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R, Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A, Lehtimäki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikäinen, Leo-Pekka, MacGregor, Stuart, Mackey, David A, Mahajan, Anubha, Mangino, Massimo, Männistö, Satu, McCarthy, Mark I, McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B, Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P, de Mutsert, Renee, Nalls, Mike A, Nedeljkovic, Ivana, North, Kari E, Pennell, Craig E, Pradhan, Aruna D, Province, Michael A, Raitakari, Olli T, Raulerson, Chelsea K, Reiner, Alex P, Ridker, Paul M, Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I, Salomaa, Veikko, Sandoval-Zárate, America A, Sitlani, Colleen M, Spector, Tim D, Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D, Thuesen, Betina, Tönjes, Anke, Uitterlinden, Andre G, Venturini, Cristina, Walker, Mark, Wang, Carol A, Wang, Shuai, Wareham, Nicholas J, Willems, Sara M, Willems van Dijk, Ko, Wilson, James G, Wu, Ying, Yao, Jie, Young, Kristin L, Langenberg, Claudia, and Frayling, Timothy M
Subjects: Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Nutrition, Obesity, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Cardiovascular, Adiponectin, Adipose Tissue, Adolescent, Adult, Black or African American, Aged, Aged, 80 and over, Exome, Female, Genetic Predisposition to Disease, Hispanic or Latino, Humans, Lipids, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, White People, Young Adult, adiponectin, cardio metabolic traits, exome, genetics, genome-wide association study, lipids, obesity, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract: Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.
Published: 2019

19. Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes

Author: Barata, Llilda, Feitosa, Mary F, Bielak, Lawrence F, Halligan, Brian, Baldridge, Abigail S, Guo, Xiuqing, Yerges‐Armstrong, Laura M, Smith, Albert V, Yao, Jie, Palmer, Nicholette D, VanWagner, Lisa B, Carr, J Jeffrey, Chen, Yii‐Der I, Allison, Matthew, Budoff, Matthew J, Handelman, Samuel K, Kardia, Sharon LR, Mosley, Thomas H, Ryan, Kathleen, Harris, Tamara B, Launer, Lenore J, Gudnason, Vilmundur, Rotter, Jerome I, Fornage, Myriam, Rasmussen‐Torvik, Laura J, Borecki, Ingrid B, O’Connell, Jeffrey R, Peyser, Patricia A, Speliotes, Elizabeth K, and Province, Michael A
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Nutrition, Diabetes, Prevention, Genetics, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Liver Disease, Obesity, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Oral and gastrointestinal, Clinical sciences
Abstract: The accumulation of excess fat in the liver (hepatic steatosis) in the absence of heavy alcohol consumption causes nonalcoholic fatty liver disease (NAFLD), which has become a global epidemic. Identifying metabolic risk factors that interact with the genetic risk of NAFLD is important for reducing disease burden. We tested whether serum glucose, insulin, insulin resistance, triglyceride (TG), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index (BMI), and waist-to-hip ratio adjusted for BMI interact with genetic variants in or near the patatin-like phospholipase domain containing 3 (PNPLA3) gene, the glucokinase regulatory protein (GCKR) gene, the neurocan/transmembrane 6 superfamily member 2 (NCAN/TM6SF2) gene, and the lysophospholipase-like 1 (LYPLAL1) gene to exacerbate hepatic steatosis, estimated by liver attenuation. We performed association analyses in 10 population-based cohorts separately and then meta-analyzed results in up to 14,751 individuals (11,870 of European ancestry and 2,881 of African ancestry). We found that PNPLA3-rs738409 significantly interacted with insulin, insulin resistance, BMI, glucose, and TG to increase hepatic steatosis in nondiabetic individuals carrying the G allele. Additionally, GCKR-rs780094 significantly interacted with insulin, insulin resistance, and TG. Conditional analyses using the two largest European ancestry cohorts in the study showed that insulin levels accounted for most of the interaction of PNPLA3-rs738409 with BMI, glucose, and TG in nondiabetic individuals. Insulin, PNPLA3-rs738409, and their interaction accounted for at least 8% of the variance in hepatic steatosis in these two cohorts. Conclusion: Insulin resistance, either directly or through the resultant elevated insulin levels, more than other metabolic traits, appears to amplify the PNPLA3-rs738409-G genetic risk for hepatic steatosis. Improving insulin resistance in nondiabetic individuals carrying PNPLA3-rs738409-G may preferentially decrease hepatic steatosis.
Published: 2019

20. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

Author: Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E., Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L., Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J.M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agnes, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Schönherr, Sebastian, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Le, Phuong, Feitosa, Mary F., Wojczynski, Mary K., Hemerich, Daiane, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Noah, Tsao L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Emmel, Carina, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Sankareswaran, Alagu, Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R.H.J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Morgan, Anna, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R.B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, He, Karen Y., Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W.J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Ida Chen, Yii-Der, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D.C., Arnett, Donna K., Walker, Mark, Scott, Laura J., Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N.A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Lu, Fan, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, t Hart, Leen M., Elders, Petra J.M., Rader, Daniel J., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J.F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F.A., Kiemeney, Lambertus, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., Willems van Dijk, Ko, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Huey-Herng Sheu, Wayne, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K.E., Boomsma, Dorret I., de Geus, Eco J.C., Cupples, L. Adrienne, van Meurs, Joyce B.J., Ikram, Arfan, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Tuomilehto, Jaakko, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, Y. Eugene, Ho, Yuk-Lam, Lynch, Julie A., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Struan Grant, Natarajan, Pradeep, Sun, Yan V., Morris, Andrew P., Deloukas, Panos, Peloso, Gina, Assimes, Themistocles L., Willer, Cristen J., Zhu, Xiang, and Brown, Christopher D.
Published: 2022
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21. 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 C. Y., 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 J. Y., Tam, Claudia H. T., 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 C. N., Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Cushman, Mary, Das, Swapan K., de Silva, H. Janaka, Dedoussis, George, Dimitrov, Latchezar, Doumatey, Ayo P., Du, Shufa, Duan, Qing, Eckardt, Kai-Uwe, Emery, Leslie S., Evans, Daniel S., Evans, Michele K., Fischer, Krista, Floyd, James S., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Frayling, Timothy M., Freedman, Barry I., Fuchsberger, Christian, Genter, Pauline, Gerstein, Hertzel C., Giedraitis, Vilmantas, González-Villalpando, Clicerio, González-Villalpando, Maria Elena, Goodarzi, Mark O., Gordon-Larsen, Penny, Gorkin, David, Gross, Myron, Guo, Yu, Hackinger, Sophie, Han, Sohee, Hattersley, Andrew T., Herder, Christian, Howard, Annie-Green, Hsueh, Willa, Huang, Mengna, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Ikram, Mohammad Arfan, Ingelsson, Martin, Islam, Md Tariqul, Isono, Masato, Jang, Hye-Mi, Jasmine, Farzana, Jiang, Guozhi, Jonas, Jost B., Jørgensen, Marit E., Jørgensen, Torben, Kamatani, Yoichiro, Kandeel, Fouad R., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kaur, Varinderpal, Kawaguchi, Takahisa, Keaton, Jacob M., Kho, Abel N., Khor, Chiea-Chuen, Kibriya, Muhammad G., Kim, Duk-Hwan, Kohara, Katsuhiko, Kriebel, Jennifer, Kronenberg, Florian, Kuusisto, Johanna, Läll, Kristi, Lange, Leslie A., Lee, Myung-Shik, Lee, Nanette R., Leong, Aaron, Li, Liming, Li, Yun, Li-Gao, Ruifang, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Locke, Adam E., Louie, Tin, Luan, Jian’an, Luk, Andrea O., Luo, Xi, Lv, Jun, Lyssenko, Valeriya, Mamakou, Vasiliki, Mani, K. Radha, Meitinger, Thomas, Metspalu, Andres, Morris, Andrew D., Nadkarni, Girish N., Nadler, Jerry L., Nalls, Michael A., Nayak, Uma, Nongmaithem, Suraj S., Ntalla, Ioanna, Okada, Yukinori, Orozco, Lorena, Patel, Sanjay R., Pereira, Mark A., Peters, Annette, Pirie, Fraser J., Porneala, Bianca, Prasad, Gauri, Preissl, Sebastian, Rasmussen-Torvik, Laura J., Reiner, Alexander P., Roden, Michael, Rohde, Rebecca, Roll, Kathryn, Sabanayagam, Charumathi, Sander, Maike, Sandow, Kevin, Sattar, Naveed, Schönherr, Sebastian, Schurmann, Claudia, Shahriar, Mohammad, Shi, Jinxiu, Shin, Dong Mun, Shriner, Daniel, Smith, Jennifer A., So, Wing Yee, Stančáková, Alena, Stilp, Adrienne M., Strauch, Konstantin, Suzuki, Ken, Takahashi, Atsushi, Taylor, Kent D., Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tomlinson, Brian, Torres, Jason M., Tsai, Fuu-Jen, Tuomilehto, Jaakko, Tusie-Luna, Teresa, Udler, Miriam S., Valladares-Salgado, Adan, van Dam, Rob M., van Klinken, Jan B., Varma, Rohit, Vujkovic, Marijana, Wacher-Rodarte, Niels, Wheeler, Eleanor, Whitsel, Eric A., Wickremasinghe, Ananda R., van Dijk, Ko Willems, Witte, Daniel R., Yajnik, Chittaranjan S., Yamamoto, Ken, Yamauchi, Toshimasa, Yengo, Loïc, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Yusuf, Salim, Zhang, Liang, Zheng, Wei, Raffel, Leslie J., Igase, Michiya, Ipp, Eli, Redline, Susan, Cho, Yoon Shin, Lind, Lars, Province, Michael A., Hanis, Craig L., Peyser, Patricia A., Ingelsson, Erik, Zonderman, Alan B., Psaty, Bruce M., Wang, Ya-Xing, Rotimi, Charles N., Becker, Diane M., Matsuda, Fumihiko, Liu, Yongmei, Zeggini, Eleftheria, Yokota, Mitsuhiro, Rich, Stephen S., Kooperberg, Charles, Pankow, James S., Engert, James C., Chen, Yii-Der Ida, Froguel, Philippe, Wilson, James G., Sheu, Wayne H. H., Kardia, Sharon L. R., Wu, Jer-Yuarn, Hayes, M. Geoffrey, Ma, Ronald C. W., Wong, Tien-Yin, Groop, Leif, Mook-Kanamori, Dennis O., Chandak, Giriraj R., Collins, Francis S., Bharadwaj, Dwaipayan, Paré, Guillaume, Sale, Michèle M., Ahsan, Habibul, Motala, Ayesha A., Shu, Xiao-Ou, Park, Kyong-Soo, Jukema, J. Wouter, Cruz, Miguel, McKean-Cowdin, Roberta, Grallert, Harald, Cheng, Ching-Yu, Bottinger, Erwin P., Dehghan, Abbas, Tai, E-Shyong, Dupuis, Josée, Kato, Norihiro, Laakso, Markku, Köttgen, Anna, Koh, Woon-Puay, Palmer, Colin N. A., Liu, Simin, Abecasis, Goncalo, Kooner, Jaspal S., Loos, Ruth J. F., North, Kari E., Haiman, Christopher A., Florez, Jose C., Saleheen, Danish, Hansen, Torben, Pedersen, Oluf, Mägi, Reedik, Langenberg, Claudia, Wareham, Nicholas J., Maeda, Shiro, Kadowaki, Takashi, Lee, Juyoung, Millwood, Iona Y., Walters, Robin G., Stefansson, Kari, Myers, Simon R., Ferrer, Jorge, Gaulton, Kyle J., Meigs, James B., Mohlke, Karen L., Gloyn, Anna L., Bowden, Donald W., Below, Jennifer E., Chambers, John C., Sim, Xueling, Boehnke, Michael, Rotter, Jerome I., McCarthy, Mark I., and Morris, Andrew P.
Published: 2022
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22. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Author: Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, and Heid, Iris M.
Published: 2022
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23. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Author: Kanoni, Stavroula, Graham, Sarah E., Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L., Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J. M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Yousri, Noha A., Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, EWarwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Vazquez-Moreno, Miguel, Feitosa, Mary F., Wojczynski, Mary K., Wang, Zhe, Preuss, Michael H., Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Tsao, Noah L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Frank, Mirjam, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Bayyana, Swati, Stringham, Heather M., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Nardone, Giuseppe Giovanni, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R. B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Liang, Jingjing, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, Hollander, Anneke Iden, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Costanzo, Maria C., Jang, Dongkeun, Burtt, Noël P., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M.‘t, Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., Willemsen, Allegonda H. M., Cupples, LAdrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, YEugene, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter W. F., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Mohlke, Karen L., Sun, Yan V., Morris, Andrew P., Boehnke, Michael, Brown, Christopher D., Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J., Assimes, Themistocles L., and Peloso, Gina M.
Published: 2022
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24. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author: Crapo, James D., Silverman, Edwin K., Cummings, Sara, Madden, Kelley, Make, Barry J., Nabbosa, Juliet, Port, Emily, Rashdi, Serine, Regan, Elizabeth A., Stepp, Lori, Watts, Shandi, Weaver, Michael, Beaty, Terri, Bowler, Russell P., Curtis, Jeffrey L., Han, MeiLan K., Hokanson, John E., Lynch, David A., Strand, Matthew J., Anderson, Gary, Bleecker, Eugene R., Coxson, Harvey O., Crystal, Ronald G., Hogg, James C., Province, Michael A., Rennard, Stephen I., Croxton, Thomas, Gan, Weiniu, Postow, Lisa A., Viviano, Lisa M., Costa-Davis, Corinne, Malanga, Elisha, Prieto, Delia, Tal-Singer, Ruth, Farzadegan, Homayoon, Hadji, Akila, Sathe, Leena, Baraghoshi, David, Chen, Grace, Crooks, James, Knowles, Ruthie, Pratte, Katherine, Wilson, Carla, Zelarney, Pearlanne T., Kechris, Katerina J., Leach, Sonia, Austin, Erin E., Czizik, Annika, Kinney, Gregory, Li, Yisha, Lutz, Sharon M., Ragland, Margaret F., Richmond, Nicole, Young, Kendra A., Cho, Michael, Castaldi, Peter J., Glass, Kimberly, Hersh, Craig, Kim, Wonji, Liu, Yang-Yu, Hersh, Craig P., Bidinger, Jacqueline, Cho, Michael H., Conrad, Douglas, DeMeo, Dawn L., El-Boueiz, Adel R., Foreman, Marilyn G., Ghosh, Auyon, Hahn, Georg, Hansel, Nadia N., Hayden, Lystra P., Hobbs, Brian, Kim, Woori, Lange, Christoph, McDonald, Merry- Lynn, McGeachie, Michael, Moll, Matthew, Morris, Melody, Patsopoulos, Nikolaos A., Qiao, Dandi, Ruczinski, Ingo, Wan, Emily S., Dy, Jennifer G., Fain, Sean B., Ginsburg, Shoshana, Hoffman, Eric A., Humphries, Stephen, Judy, Philip F., Stefanie Mason, Alex Kluiber, Oh, Andrea, Poynton, Clare, Reinhardt, Joseph M., Ross, James, San Jose Estepar, Raul, Schroeder, Joyce D., Sitek, Arkadiusz, Steiner, Robert M., van Beek, Edwin, Ginneken, Bram van, van Rikxoort, Eva, Washko, George R., Jensen, Robert, John E. Hokanson, Co-Chair, Bhatt, Surya P., Casaburi, Richard, Kim, Victor, Putcha, Nirupama, Han, MeiLan, Bon, Jessica, Diaz, Alejandro A., Regan, Elizabeth, Anzueto, Antonio, Bailey, William C., Criner, Gerard J., Dransfield, Mark T., Kinney, Greg, Sprenger, Kim, Benos, Takis, Hanania, Nicola A., Hoth, Karin F., Lambert, Allison, Lowe, Katherine, Oates, Gabriela, Parekh, Trisha, Westney, Gloria, Young, Kendra, Balasubramanian, Aparna, Boriek, Aladin, Fawzy, Ashraf, Jacobson, Francine, LaFon, David C., MacIntyre, Neil, Maselli-Caceres, Diego, McCormack, Meredith C., McDonald, Merry-Lynn, Sciurba, Frank, Soler, Xavier, Tejwani, Vickram, van Beek, Edwin JR., Wade, Raymond C., Wells, Mike, Wendt, Chris H., Yun, Jeong H., Zhang, Jingzhou, Gillenwater, Lucas, Lowe, Katherine E., Pratte, Katherine A., Ragland, Margaret, Attaway, Amy, Mason, Stefanie, Rossiter, Harry B., Saha, Punam Kumar, Wilson, Ava, Amaza, Hannatu, Baldomero, Adrienne, Mamary, A. James, O’Brien, James, Wise, Robert A., Eakin, Michelle, Fiedorowicz, Jess G., Henkle, Ben, Holm, Kristen, Iyer, Anand, Kunisaki, Ken M., McEvoy, Charlene, Mkorombindo, Takudzwa, Shinozaki, Gen, Yohannes, Abebaw, Hobbs, Brian D., Miller, Bruce E., Retson, Tara, McCloskey, Lisa, Pernicano, Perry G., Atik, Mustafa, Bertrand, Laura, Monaco, Thomas, Narendra, Dharani, Lenge de Rosen, Veronica V., Badu-Danso, Kwame, Jacobson, Francine L., Kaufman, Laura, Maguire, Cherie, Struble, Sophie, Wilson, Seth, Barr, R. Graham, Almonte, Casandra, Austin, John H.M., Gomez Blum, Maria Lorena, D’Souza, Belinda M., Florez, Emilay, Martinez, Rodney, MacIntyre, Neil, Jr., Curry, Wendy, McAdams, H. Page, Reikofski, Charlotte V., Washington, Lacey, Brown, Robert, Clare, Cheryl, Daniel, Marie, Horton, Karen, Ting “Tony” Lin, Cheng, Mirza, Tahira, Scott, Meagan, Shade, Becky, Budoff, Matt, Calmelat, Robert, Cavanaugh, Deborah, Dailing, Chris, Diaz, Leticia, Fischer, Hans, Indelicato, Renee Love, Porszasz, Janos, Soriano, April, Stringer, William, Urrutia, Miriam, Baldomero, Arianne, Bell, Brian, Deconcini, Miranda, Loes, Linda, Phelan, Jonathan, Robichaux, Camille, Sasse, Cheryl, Tashjian, Joseph H., Flenaugh, Eric L., Abson, Kema, Gebrekristos, Hirut, Johnson, Priscilla, Jordan, Jessica, Ponce, Mario, Terpenning, Silanath, Wilson, Derrick, Broadhurst, Grace, Dyer, Debra, Engel, Elena, Finigan, Jay, Hill, Andrew, Jones, Alex, Jones, Ryan, Owen, Jordan, Rosiello, Richard, Andries, Nicole, Charpentier, Mary, Kirk, Diane, Pace, David, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Davis, Valena, Desai, Parag, Fehrle, Dee, Grabianowski, Carla, Jacobs, Michael, Jameson, Laurie, Jones, Gayle M., Kelsen, Steven, Marchetti, Nathaniel, McGonagle, Francine, Satti, Aditi, Shenoy, Kartik, Sheridan, Regina, Vega-Sanchez, Maria, Wallace, Samantha, Akinseye-kolapo, Samuel, Baker, Matthew, Goggins, Arnissa, McClain, Anny, Nath, Hrudaya, Singh, Satinder P., Sonavane, Sushil K., Westfall, Elizabeth, Gil, Marissa, El Hajjaoui, Tarek, Hsiao, Albert, Martineau, Amber, Mielke, Jenna, Perez, Karl, Querido, Gabriel, Reston, Tara, Yen, Andrew, Comellas, Alejandro, Fortis, Spyridon, Galizia, Mauricio, Garcia, Eric, Keating, Janet, Laroia, Archana, Lee, Changhyun, Meyer, Amber, Mullan, Brian, Nagpal, Prashant, Ofori, Oloigbe, Suiter, Sierra, Mason, Stefanie E., Moreta-Martinez, Rafael, Labaki, Wassim W., San Jose Estepar, Ruben, Make, Barry, and Stringer, Kathleen
Published: 2022
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25. Discovery of genomic and transcriptomic pleiotropy between kidney function and soluble receptor for advanced glycation end products using correlated meta‐analyses: The Long Life Family Study.

Author: Feitosa, Mary F., Lin, Shiow J., Acharya, Sandeep, Thyagarajan, Bharat, Wojczynski, Mary K., Kuipers, Allison L., Kulminski, Alexander, Christensen, Kaare, Zmuda, Joseph M., Brent, Michael R., and Province, Michael A.
Subjects: ADVANCED glycation end-products, KIDNEY tubules, CHRONIC kidney failure, CYSTATIN C, GENE expression
Abstract: Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end‐products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole‐genome sequencing and correlated meta‐analyses on combined genome‐wide association study (GWAS) p‐values in 4182 individuals (age range: 24–110) from the Long Life Family Study (LLFS). We also conducted transcriptome‐wide association studies (TWAS) on whole blood in a subset of 1209 individuals. We identified 59 pleiotropic GWAS loci (p < 5 × 10−8) and 17 TWAS genes (Bonferroni‐p < 2.73 × 10−6) for eGFR traits and sRAGE. TWAS genes, LSP1 and MIR23AHG, were associated with eGFR and sRAGE located within GWAS loci, lncRNA‐KCNQ1OT1 and CACNA1A/CCDC130, respectively. GWAS variants were eQTLs in the kidney glomeruli and tubules, and GWAS genes predicted kidney carcinoma. TWAS genes harbored eQTLs in the kidney, predicted kidney carcinoma, and connected enhancer‐promoter variants with kidney function‐related phenotypes at p < 5 × 10−8. Additionally, higher allele frequencies of protective variants for eGFR traits were detected in LLFS than in ALFA‐Europeans and TOPMed, suggesting better kidney function in healthy‐aging LLFS than in general populations. Integrating genomic annotation and transcriptional gene activity revealed the enrichment of genetic elements in kidney function and aging‐related processes. The identified pleiotropic loci and gene expressions for eGFR and sRAGE suggest their underlying shared genetic effects and highlight their roles in kidney‐ and aging‐related signaling pathways. [ABSTRACT FROM AUTHOR]
Published: 2024
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26. A microbiome-directed therapeutic food for children recovering from severe acute malnutrition.

Author: Hartman, Steven J., Hibberd, Matthew C., Mostafa, Ishita, Naila, Nurun N., Islam, Md. Munirul, Zaman, Mahabub Uz, Huq, Sayeeda, Mahfuz, Mustafa, Islam, Md. Tazul, Mukherji, Kallol, Moghaddam, Vaha Akbary, Chen, Robert Y., Province, Michael A., Webber, Daniel M., Henrissat, Suzanne, Henrissat, Bernard, Terrapon, Nicolas, Rodionov, Dmitry A., Osterman, Andrei L., and Barratt, Michael J.
Subjects: CHILD nutrition, CENTRAL nervous system, BLOOD proteins, RANDOMIZED controlled trials, BACTERIAL genomes
Abstract: Globally, severe acute malnutrition (SAM), defined as a weight-for-length z-score more than three SDs below a reference mean (WLZ < −3), affects 14 million children under 5 years of age. Complete anthropometric recovery after standard, short-term interventions is rare, with children often left with moderate acute malnutrition (MAM; WLZ −2 to −3). We conducted a randomized controlled trial (RCT) involving 12- to 18-month-old Bangladeshi children from urban and rural sites, who, after initial hospital-based treatment for SAM, received a 3-month intervention with a microbiome-directed complementary food (MDCF-2) or a calorically more dense, standard ready-to-use supplementary food (RUSF). The rate of WLZ improvement was significantly greater in MDCF-2–treated children (P = 8.73 × 10−3), similar to our previous RCT of Bangladeshi children with MAM without antecedent SAM (P = 0.032). A correlated meta-analysis of plasma levels of 4520 proteins in both RCTs revealed 215 positively associated with WLZ (largely representing musculoskeletal and central nervous system development) and 44 negatively associated (primarily related to immune activation). Moreover, the positively associated proteins were significantly enriched by MDCF-2 (q = 1.1 × 10−6). Characterizing the abundances of 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome and how, during treatment for MAM, specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and anthropometric recovery. These results provide a rationale for further testing the generalizability of MDCF efficacy and for identifying biomarkers to define treatment responses. Editor's summary: Severe acute malnutrition affects millions of children worldwide. Hartman et al. performed a 3-month randomized controlled trial of a gut microbiome–directed food supplement in 12- to 18-month-old Bangladeshi children living in rural and urban locations with moderate acute malnutrition and who had already been treated in hospital for severe acute malnutrition. Their microbiome-directed complementary food (MDCF-2) improved ponderal growth better than a more calorically dense, commonly used supplement and increased plasma abundance of proteins involved in musculoskeletal and central nervous system development. The authors tied the improvements in the children's health to changes in growth-associated gut microbiome species, most notably Prevotella copri strains and their carbohydrate degrading pathways. —Catherine Charneski [ABSTRACT FROM AUTHOR]
Published: 2024
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27. The Long Life Family Study (LLFS)

Author: Wojczynski, Mary K., Province, Michael A., Dupre, Matthew E., Section editor, Gu, Danan, editor, and Dupre, Matthew E., editor
Published: 2021
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28. The power of genetic diversity in genome-wide association studies of lipids

Author: Graham, Sarah E., Clarke, Shoa L., Wu, Kuan-Han H., Kanoni, Stavroula, Zajac, Greg J. M., Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R., Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C., Hunt, Karen A., Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Ruotsalainen, Sanni E., Havulinna, Aki S., Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A., Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A., Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Hindy, George, Rasheed, Asif, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Willemsen, Gonneke, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Yao, Jie, Manichaikul, Ani, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Sidore, Carlo, Fiorillo, Edoardo, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Thuesen, Betina H., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Feitosa, Mary F., Wojczynski, Mary K., Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Kember, Rachel L., Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L., Marten, Jonathan, Schmidt, Börge, Arendt, Marina, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U., Yousri, Noha A., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Chai, Xiaoran, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Hung, Yi-Jen, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Gorski, Mathias, Brumat, Marco, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Xue, Chao, Zhang, Jifeng, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., Lee, Jiwon, van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Zimmermann, Martina E., Lee, Jong Young, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hildalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Schwander, Karen, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Highland, Heather M., Young, Kristin L., Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Nadkarni, Girish N., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, Konain Fatima, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Chen, Y. Eugene, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Jung, Bettina, Böger, Carsten A., Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Yajnik, Chittaranjan S., Mercader, Josep M., Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Lu, Fan, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Parra, Esteban J., Cruz, Miguel, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, ’t Hart, Leen M., Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Cucca, Francesco, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., de Geus, Eco J. C., Cupples, L. Adrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Justice, Anne E., Baras, Aris, Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Thorsteinsdottir, Unnur, Stefansson, Kari, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Rotimi, Charles N., Hazelhurst, Scott, Ramsay, Michèle, Trembath, Richard C., van Heel, David A., Tamiya, Gen, Yamamoto, Masayuki, Kim, Bong-Jo, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Natarajan, Pradeep, Peloso, Gina M., Brown, Christopher D., Morris, Andrew P., Assimes, Themistocles L., Deloukas, Panos, Sun, Yan V., and Willer, Cristen J.
Published: 2021
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29. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Author: Wyss, Annah B, Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N, Lahousse, Lies, Latourelle, Jeanne C, Smith, Albert Vernon, Bartz, Traci M, Feitosa, Mary F, Gao, Wei, Ahluwalia, Tarunveer S, Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K, Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E, Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D, Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M, Hu, Donglei, Mogil, Lauren S, Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B, Kalhan, Ravi, Heckbert, Susan R, Paternoster, Lavinia, Burkart, Kristin M, Liu, Yongmei, Holliday, Elizabeth G, Wilson, James G, Vonk, Judith M, Sanders, Jason L, Barr, R Graham, de Mutsert, Renée, Menezes, Ana Maria Baptista, Adams, Hieab HH, van den Berge, Maarten, Joehanes, Roby, Levin, Albert M, Liberto, Jennifer, Launer, Lenore J, Morrison, Alanna C, Sitlani, Colleen M, Celedón, Juan C, Kritchevsky, Stephen B, Scott, Rodney J, Christensen, Kaare, Rotter, Jerome I, Bonten, Tobias N, Wehrmeister, Fernando César, Bossé, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A, Kaplan, Robert C, Lohman, Kurt, McEvoy, Mark, Province, Michael A, Rosendaal, Frits R, Taylor, Kent D, Nickle, David C, Williams, L Keoki, Burchard, Esteban G, Wheeler, Heather E, Sin, Don D, Gudnason, Vilmundur, North, Kari E, Fornage, Myriam, Psaty, Bruce M, Myers, Richard H, O'Connor, George, Hansen, Torben, Laurie, Cathy C, Cassano, Patricia A, Sung, Joohon, Kim, Woo Jin, Attia, John R, Lange, Leslie, Boezen, H Marike, Thyagarajan, Bharat, Rich, Stephen S, Mook-Kanamori, Dennis O, Horta, Bernardo Lessa, Uitterlinden, André G, Im, Hae Kyung, Cho, Michael H, Brusselle, Guy G, and Gharib, Sina A
Subjects: Lung, Humans, Lung Diseases, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Vital Capacity, Forced Expiratory Volume, Regression Analysis, Sample Size, Smoking, Genomics, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, African Continental Ancestry Group, Asian Americans, European Continental Ancestry Group, Hispanic Americans, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive
Abstract: Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.
Published: 2018

30. Genome‐Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Author: Smith, Caren E, Follis, Jack L, Dashti, Hassan S, Tanaka, Toshiko, Graff, Mariaelisa, Fretts, Amanda M, Kilpeläinen, Tuomas O, Wojczynski, Mary K, Richardson, Kris, Nalls, Mike A, Schulz, Christina‐Alexandra, Liu, Yongmei, Frazier‐Wood, Alexis C, van Eekelen, Esther, Wang, Carol, de Vries, Paul S, Mikkilä, Vera, Rohde, Rebecca, Psaty, Bruce M, Hansen, Torben, Feitosa, Mary F, Lai, Chao‐Qiang, Houston, Denise K, Ferruci, Luigi, Ericson, Ulrika, Wang, Zhe, de Mutsert, Renée, Oddy, Wendy H, de Jonge, Ester AL, Seppälä, Ilkka, Justice, Anne E, Lemaitre, Rozenn N, Sørensen, Thorkild IA, Province, Michael A, Parnell, Laurence D, Garcia, Melissa E, Bandinelli, Stefania, Orho‐Melander, Marju, Rich, Stephen S, Rosendaal, Frits R, Pennell, Craig E, Jong, Jessica C Kiefte‐de, Kähönen, Mika, Young, Kristin L, Pedersen, Oluf, Aslibekyan, Stella, Rotter, Jerome I, Mook‐Kanamori, Dennis O, Zillikens, M Carola, Raitakari, Olli T, North, Kari E, Overvad, Kim, Arnett, Donna K, Hofman, Albert, Lehtimäki, Terho, Tjønneland, Anne, Uitterlinden, André G, Rivadeneira, Fernando, Franco, Oscar H, German, J Bruce, Siscovick, David S, Cupples, L Adrienne, and Ordovás, José M
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Genetics, Prevention, Nutrition, Obesity, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Cancer, Metabolic and endocrine, Actins, Adult, Aged, Body Mass Index, Cohort Studies, Cross-Sectional Studies, Dairy Products, Female, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Myosin-Light-Chain Phosphatase, Polymorphism, Single Nucleotide, White People, body mass index, CHARGE consortium, dairy intake, genome-wide interaction study, meta-analysis, Food Sciences, Public Health and Health Services, Food Science, Nutrition & Dietetics, Food sciences, Nutrition and dietetics
Abstract: ScopeBody weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.Methods and resultsA genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction
Published: 2018

31. Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies

Author: Huang, Tao, Ding, Ming, Bergholdt Helle, KM, Wang, Tiange, Heianza, Yoriko, Sun, Dianjianyi, Frazier-Wood Alexis, C, Aslibekyan, Stella, North Kari, E, Voortman, Trudy, Graff, Mariaelisa, Smith Caren, E, Lai, Chao-Qiang, Varbo, Anette, Lemaitre, Rozenn N, de Jonge, M Ester AL, Fumeron, Frédéric, Corella, Dolores, Wang, Carol A, Tjønneland, Anne, Overvad, Kim, Sørensen, Thorkild IA, Feitosa, Mary F, Wojczynski, Mary K, Kähönen, Mika, Renström, Frida, Psaty, Bruce M, Siscovick, David S, Barroso, Inês, Johansson, Ingegerd, Hernandez, Dena, Ferrucci, Luigi, Bandinelli, Stefania, Linneberg, Allan, Zillikens, M Carola, Sandholt, Camilla Helene, Pedersen, Oluf, Hansen, Torben, Schulz, Christina-Alexandra, Sonestedt, Emily, Orho-Melander, Marju, Chen, Tzu-An, Rotter, Jerome I, Allison, Mathew A, Rich, Stephen S, Sorlí, Jose V, Coltell, Oscar, Pennell, Craig E, Eastwood, Peter, Hofman, Albert, Uitterlinden, Andre G, van Rooij, Frank JA, Chu, Audrey Y, Rose, Lynda M, Ridker, Paul M, Viikari, Jorma, Raitakari, Olli, Lehtimäki, Terho, Mikkilä, Vera, Willett, Walter C, Wang, Yujie, Tucker, Katherine L, Ordovas, Jose M, Kilpeläinen, Tuomas O, Province, Michael A, Franks, Paul W, Arnett, Donna K, Tanaka, Toshiko, Toft, Ulla, Ericson, Ulrika, Franco, Oscar H, Mozaffarian, Dariush, Hu, Frank B, Chasman, Daniel I, Nordestgaard, Børge G, Ellervik, Christina, and Qi, Lu
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Genetics, Adult, Body Mass Index, Body Weight, Cross-Sectional Studies, Dairy Products, Genotype, Humans, Mendelian Randomization Analysis, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Prospective Studies, Mendelian Randomization of Dairy Consumption Working Group, Medical Biotechnology, Medical Biochemistry and Metabolomics, Clinical Sciences, General Clinical Medicine, Clinical sciences, Medical biochemistry and metabolomics
Abstract: BackgroundAssociations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.MethodsWe performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.ResultsHigher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00-0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14-0.25) serving/day higher dairy intake (P = 3.15 × 10-12) and 0.12 (95% CI, 0.06-0.17) kg/m2 higher BMI (P = 2.11 × 10-5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27-0.92; P = 3.0 × 10-4).ConclusionsThe present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
Published: 2018

32. A Paradigm For Calling Sequence In Families: The Long Life Family Study

Author: Daw, E Warwick, primary, Anema, Jason A, additional, Schwander, Karen, additional, Lin, Shiow Jiuan, additional, Wang, Lihua, additional, Wojczynski, Mary, additional, Thyagarajan, Bharat, additional, Stitziel, Nathan O, additional, and Province, Michael A, additional
Published: 2024
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33. PathFinder: a novel graph transformer model to infer multi-cell intra- and inter-cellular signaling pathways and communications

Author: Feng, Jiarui, primary, Song, Haoran, additional, Province, Michael, additional, Li, Guangfu, additional, Payne, Philip R. O., additional, Chen, Yixin, additional, and Li, Fuhai, additional
Published: 2024
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34. A Novel Gene ARHGAP44 for Longitudinal Changes in Glycated Hemoglobin (HbA1c) in Subjects without Type 2 Diabetes: Evidence from the Long Life Family Study (LLFS) and the Framingham Offspring Study (FOS)

Author: Wang, Siyu, primary, Lenzini, Petra, additional, Thygarajan, Bharat, additional, Lee, Joseph H., additional, Vardarajan, Badri N., additional, Yashin, Anatoli, additional, Miljkovic, Iva, additional, Daw, E. Warwick, additional, Lin, Shiow J., additional, Patti, Gary, additional, Brent, Michael, additional, Zmuda, Joseph M., additional, Perls, Thomas T., additional, Christensen, Kaare, additional, Province, Michael A., additional, and An, Ping, additional
Published: 2024
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35. Developmental origins of exceptional health and survival: A four-generation family cohort study

Author: Keys, Matthew Thomas, primary, Pedersen, Dorthe Almind, additional, Larsen, Pernille Stemann, additional, Kulminski, Alexander, additional, Feitosa, Mary, additional, Wojczcynski, Mary, additional, Province, Michael, additional, and Christensen, Kaare, additional
Published: 2024
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36. 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

37. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

Author: Natarajan, Pradeep, Bis, Joshua C, Bielak, Lawrence F, Cox, Amanda J, Dörr, Marcus, Feitosa, Mary F, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, Isaacs, Aaron, Jhun, Min A, Kavousi, Maryam, Li-Gao, Ruifang, Lyytikäinen, Leo-Pekka, Marioni, Riccardo E, Schminke, Ulf, Stitziel, Nathan O, Tada, Hayato, van Setten, Jessica, Smith, Albert V, Vojinovic, Dina, Yanek, Lisa R, Yao, Jie, Yerges-Armstrong, Laura M, Amin, Najaf, Baber, Usman, Borecki, Ingrid B, Carr, J Jeffrey, Chen, Yii-Der Ida, Cupples, L Adrienne, de Jong, Pim A, de Koning, Harry, de Vos, Bob D, Demirkan, Ayse, Fuster, Valentin, Franco, Oscar H, Goodarzi, Mark O, Harris, Tamara B, Heckbert, Susan R, Heiss, Gerardo, Hoffmann, Udo, Hofman, Albert, Išgum, Ivana, Jukema, J Wouter, Kähönen, Mika, Kardia, Sharon LR, Kral, Brian G, Launer, Lenore J, Massaro, Joe, Mehran, Roxana, Mitchell, Braxton D, Mosley, Thomas H, de Mutsert, Renée, Newman, Anne B, Nguyen, Khanh-Dung, North, Kari E, O'Connell, Jeffrey R, Oudkerk, Matthijs, Pankow, James S, Peloso, Gina M, Post, Wendy, Province, Michael A, Raffield, Laura M, Raitakari, Olli T, Reilly, Dermot F, Rivadeneira, Fernando, Rosendaal, Frits, Sartori, Samantha, Taylor, Kent D, Teumer, Alexander, Trompet, Stella, Turner, Stephen T, Uitterlinden, Andre G, Vaidya, Dhananjay, van der Lugt, Aad, Völker, Uwe, Wardlaw, Joanna M, Wassel, Christina L, Weiss, Stefan, Wojczynski, Mary K, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Bowden, Donald W, Deary, Ian J, Dehghan, Abbas, Felix, Stephan B, Gudnason, Vilmundur, Lehtimäki, Terho, Mathias, Rasika, Mook-Kanamori, Dennis O, Psaty, Bruce M, Rader, Daniel J, Rotter, Jerome I, Wilson, James G, van Duijn, Cornelia M, Völzke, Henry, Kathiresan, Sekar, Peyser, Patricia A, and O'Donnell, Christopher J
Subjects: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease - Coronary Heart Disease, Aging, Human Genome, Atherosclerosis, Cardiovascular, Heart Disease, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Apolipoprotein B-100, Apolipoprotein E2, Asymptomatic Diseases, Black People, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cholesterol, LDL, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Exome, Gene Frequency, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Odds Ratio, Oligonucleotide Array Sequence Analysis, Phenotype, Prognosis, Risk Assessment, Risk Factors, Vascular Calcification, White People, carotid intima-media thickness, coronary artery calcification, exome, genome-wide association study, genomics, CHARGE Consortium, carotid intima–media thickness, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract: BackgroundThe burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease.Methods and resultsWe studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima-media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima-media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC (P=3×10-10). The APOE ε2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC (P=1×10-12) and 1.4% reduced carotid intima-media thickness (P=4×10-14) in carriers compared with noncarriers. In secondary analyses conditioning on low-density lipoprotein cholesterol concentration, the ε2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of ε2 was associated with reduced risk for coronary heart disease (odds ratio 0.77; P=1×10-11).ConclusionsExome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE ε2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.
Published: 2016

38. PathFinder: a novel graph transformer model to infer multi-cell intra- and inter-cellular signaling pathways and communications.

Author: Jiarui Feng, Haoran Song, Province, Michael, Guangfu Li, Payne, Philip R. O., Yixin Chen, and Fuhai Li
Subjects: TRANSFORMER models, SIGNALS & signaling, CELLULAR signal transduction, GRAPH neural networks, ALZHEIMER'S disease
Abstract: Recently, large-scale scRNA-seq datasets have been generated to understand the complex signaling mechanisms within the microenvironment of Alzheimer's Disease (AD), which are critical for identifying novel therapeutic targets and precision medicine. However, the background signaling networks are highly complex and interactive. It remains challenging to infer the core intra- and intermulti-cell signaling communication networks using scRNA-seq data. In this study, we introduced a novel graph transformer model, PathFinder, to infer multicell intra- and inter-cellular signaling pathways and communications among multi-cell types. Compared with existing models, the novel and unique design of PathFinder is based on the divide-and-conquer strategy. This model divides complex signaling networks into signaling paths, which are then scored and ranked using a novel graph transformer architecture to infer intra- and inter-cell signaling communications. We evaluated the performance of PathFinder using two scRNA-seq data cohorts. The first cohort is an APOE4 genotype-specific AD, and the second is a human cirrhosis cohort. The evaluation confirms the promising potential of using PathFinder as a general signaling network inference model. [ABSTRACT FROM AUTHOR]
Published: 2024
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39. Gene discovery for high-density lipoprotein cholesterol level change over time in prospective family studies

Author: Feitosa, Mary F., Lunetta, Kathryn L., Wang, Lihua, Wojczynski, Mary K., Kammerer, Candace M., Perls, Thomas, Schupf, Nicole, Christensen, Kaare, Murabito, Joanne M., and Province, Michael A.
Published: 2020
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40. An Empirical Comparison of Joint and Stratified Frameworks for Studying G × E Interactions: Systolic Blood Pressure and Smoking in the CHARGE Gene‐Lifestyle Interactions Working Group

Author: Sung, Yun Ju, Winkler, Thomas W, Manning, Alisa K, Aschard, Hugues, Gudnason, Vilmundur, Harris, Tamara B, Smith, Albert V, Boerwinkle, Eric, Brown, Michael R, Morrison, Alanna C, Fornage, Myriam, Lin, Li-An, Richard, Melissa, Bartz, Traci M, Psaty, Bruce M, Hayward, Caroline, Polasek, Ozren, Marten, Jonathan, Rudan, Igor, Feitosa, Mary F, Kraja, Aldi T, Province, Michael A, Deng, Xuan, Fisher, Virginia A, Zhou, Yanhua, Bielak, Lawrence F, Smith, Jennifer, Huffman, Jennifer E, Padmanabhan, Sandosh, Smith, Blair H, Ding, Jingzhong, Liu, Yongmei, Lohman, Kurt, Bouchard, Claude, Rankinen, Tuomo, Rice, Treva K, Arnett, Donna, Schwander, Karen, Guo, Xiuqing, Palmas, Walter, Rotter, Jerome I, Alfred, Tamuno, Bottinger, Erwin P, Loos, Ruth JF, Amin, Najaf, Franco, Oscar H, van Duijn, Cornelia M, Vojinovic, Dina, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Kardia, Sharon, Zhu, Xiaofeng, Rice, Kenneth, Borecki, Ingrid B, Rao, Dabeeru C, Gauderman, W James, and Cupples, L Adrienne
Subjects: Epidemiology, Biological Sciences, Health Sciences, Genetics, Clinical Research, Human Genome, Blood Pressure, Cohort Studies, Databases, Factual, Family, Gene Frequency, Gene-Environment Interaction, Genome-Wide Association Study, Genotype, Humans, Phenotype, Smoking, gene-environment interaction, meta-analysis, low-frequency variants, Public Health and Health Services
Abstract: Studying gene-environment (G × E) interactions is important, as they extend our knowledge of the genetic architecture of complex traits and may help to identify novel variants not detected via analysis of main effects alone. The main statistical framework for studying G × E interactions uses a single regression model that includes both the genetic main and G × E interaction effects (the "joint" framework). The alternative "stratified" framework combines results from genetic main-effect analyses carried out separately within the exposed and unexposed groups. Although there have been several investigations using theory and simulation, an empirical comparison of the two frameworks is lacking. Here, we compare the two frameworks using results from genome-wide association studies of systolic blood pressure for 3.2 million low frequency and 6.5 million common variants across 20 cohorts of European ancestry, comprising 79,731 individuals. Our cohorts have sample sizes ranging from 456 to 22,983 and include both family-based and population-based samples. In cohort-specific analyses, the two frameworks provided similar inference for population-based cohorts. The agreement was reduced for family-based cohorts. In meta-analyses, agreement between the two frameworks was less than that observed in cohort-specific analyses, despite the increased sample size. In meta-analyses, agreement depended on (1) the minor allele frequency, (2) inclusion of family-based cohorts in meta-analysis, and (3) filtering scheme. The stratified framework appears to approximate the joint framework well only for common variants in population-based cohorts. We conclude that the joint framework is the preferred approach and should be used to control false positives when dealing with low-frequency variants and/or family-based cohorts.
Published: 2016

41. 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

42. MULTI OMICS LANDSCAPE OF INSULIN SENSITIVITY IN HEALTHY OLDER PEOPLE FROM THE LONG LIFE FAMILY STUDY COHORT

Author: Moghaddam, Vaha Akbary, primary, Liao, Shu, additional, Thyagarajan, Bharat, additional, Christensen, Kaare, additional, Patti, Gary, additional, Brent, Michael, additional, Province, Michael, additional, and An, Ping, additional
Published: 2023
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43. Examination of Genetic Risk Factors for Alzheimer’s Disease in a Cohort of Familial Longevity: the Long Life Family Study

Author: Xicota, Laura, primary, Cheng, Rong, additional, Barral, Sandra, additional, Honig, Lawrence S., additional, Schupf, Nicole, additional, Gu, Yian, additional, Cosentino, Stephanie, additional, Zmuda, Joseph M, additional, Perls, Thomas T., additional, Christensen, Kaare, additional, Province, Michael A, additional, and Lee, Joseph H., additional
Published: 2023
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44. GENETIC PLEIOTROPY OF KIDNEY FUNCTION AND SOLUBLE RECEPTOR FOR AGE: THE LONG LIFE FAMILY STUDY

Author: Feitosa, Mary, primary, Jin, Shiow, additional, Acharya, Sandeep, additional, Wojczynski, Mary, additional, Christensen, Kaare, additional, Zmuda, Joseph, additional, Brent, Michael, additional, and Province, Michael, additional
Published: 2023
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45. MULTI-OMICS INTEGRATION IDENTIFIES GENES INFLUENCING TRAITS ASSOCIATED WITH CARDIOVASCULAR RISKS

Author: Acharya, Sandeep, primary, Liao, Shu, additional, Jung, Woo Seok, additional, Kang, Edward, additional, Moghaddam, Vaha Akbary, additional, Feitosa, Mary, additional, Province, Michael, additional, and Brent, Michael, additional
Published: 2023
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46. NOVEL GENE VARIANTS ASSOCIATED WITH HBA1C CHANGES OVER TIME AMONG NONDIABETIC SUBJECTS IN THE LONG LIFE FAMILY STUDY

Author: Wang, Siyu, primary, Thyagarajan, Bharat, additional, Lee, Joseph, additional, Zmuda, Joseph, additional, Christensen, Kaare, additional, Province, Michael, additional, and An, Ping, additional
Published: 2023
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47. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author: Lagou, Vasiliki, Mägi, Reedik, Hottenga, Jouke- Jan, Grallert, Harald, Perry, John R. B., Bouatia-Naji, Nabila, Marullo, Letizia, Rybin, Denis, Jansen, Rick, Min, Josine L., Dimas, Antigone S., Ulrich, Anna, Zudina, Liudmila, Gådin, Jesper R., Jiang, Longda, Faggian, Alessia, Bonnefond, Amélie, Fadista, Joao, Stathopoulou, Maria G., Isaacs, Aaron, Willems, Sara M., Navarro, Pau, Tanaka, Toshiko, Jackson, Anne U., Montasser, May E., O’Connell, Jeff R., Bielak, Lawrence F., Webster, Rebecca J., Saxena, Richa, Stafford, Jeanette M., Pourcain, Beate St, Timpson, Nicholas J., Salo, Perttu, Shin, So-Youn, Amin, Najaf, Smith, Albert V., Li, Guo, Verweij, Niek, Goel, Anuj, Ford, Ian, Johnson, Paul C. D., Johnson, Toby, Kapur, Karen, Thorleifsson, Gudmar, Strawbridge, Rona J., Rasmussen-Torvik, Laura J., Esko, Tõnu, Mihailov, Evelin, Fall, Tove, Fraser, Ross M., Mahajan, Anubha, Kanoni, Stavroula, Giedraitis, Vilmantas, Kleber, Marcus E., Silbernagel, Günther, Meyer, Julia, Müller-Nurasyid, Martina, Ganna, Andrea, Sarin, Antti-Pekka, Yengo, Loic, Shungin, Dmitry, Luan, Jian’an, Horikoshi, Momoko, An, Ping, Sanna, Serena, Boettcher, Yvonne, Rayner, N. William, Nolte, Ilja M., Zemunik, Tatijana, Iperen, Erik van, Kovacs, Peter, Hastie, Nicholas D., Wild, Sarah H., McLachlan, Stela, Campbell, Susan, Polasek, Ozren, Carlson, Olga, Egan, Josephine, Kiess, Wieland, Willemsen, Gonneke, Kuusisto, Johanna, Laakso, Markku, Dimitriou, Maria, Hicks, Andrew A., Rauramaa, Rainer, Bandinelli, Stefania, Thorand, Barbara, Liu, Yongmei, Miljkovic, Iva, Lind, Lars, Doney, Alex, Perola, Markus, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Bennett, Amanda J., Groves, Christopher J., Herder, Christian, Koistinen, Heikki A., Kinnunen, Leena, Faire, Ulf de, Bakker, Stephan J. L., Uusitupa, Matti, Palmer, Colin N. A., Jukema, J. Wouter, Sattar, Naveed, Pouta, Anneli, Snieder, Harold, Boerwinkle, Eric, Pankow, James S., Magnusson, Patrik K., Krus, Ulrika, Scapoli, Chiara, de Geus, Eco J. C. N., Blüher, Matthias, Wolffenbuttel, Bruce H. R., Province, Michael A., Abecasis, Goncalo R., Meigs, James B., Hovingh, G. Kees, Lindström, Jaana, Wilson, James F., Wright, Alan F., Dedoussis, George V., Bornstein, Stefan R., Schwarz, Peter E. H., Tönjes, Anke, Winkelmann, Bernhard R., Boehm, Bernhard O., März, Winfried, Metspalu, Andres, Price, Jackie F., Deloukas, Panos, Körner, Antje, Lakka, Timo A., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Bergman, Richard N., Tuomilehto, Jaakko, Wareham, Nicholas J., Langenberg, Claudia, Männistö, Satu, Franks, Paul W., Hayward, Caroline, Vitart, Veronique, Kaprio, Jaakko, Visvikis-Siest, Sophie, Balkau, Beverley, Altshuler, David, Rudan, Igor, Stumvoll, Michael, Campbell, Harry, van Duijn, Cornelia M., Gieger, Christian, Illig, Thomas, Ferrucci, Luigi, Pedersen, Nancy L., Pramstaller, Peter P., Boehnke, Michael, Frayling, Timothy M., Shuldiner, Alan R., Peyser, Patricia A., Kardia, Sharon L. R., Palmer, Lyle J., Penninx, Brenda W., Meneton, Pierre, Harris, Tamara B., Navis, Gerjan, Harst, Pim van der, Smith, George Davey, Forouhi, Nita G., Loos, Ruth J. F., Salomaa, Veikko, Soranzo, Nicole, Boomsma, Dorret I., Groop, Leif, Tuomi, Tiinamaija, Hofman, Albert, Munroe, Patricia B., Gudnason, Vilmundur, Siscovick, David S., Watkins, Hugh, Lecoeur, Cecile, Vollenweider, Peter, Franco-Cereceda, Anders, Eriksson, Per, Jarvelin, Marjo-Riitta, Stefansson, Kari, Hamsten, Anders, Nicholson, George, Karpe, Fredrik, Dermitzakis, Emmanouil T., Lindgren, Cecilia M., McCarthy, Mark I., Froguel, Philippe, Kaakinen, Marika A., Lyssenko, Valeriya, Watanabe, Richard M., Ingelsson, Erik, Florez, Jose C., Dupuis, Josée, Barroso, Inês, Morris, Andrew P., and Prokopenko, Inga
Published: 2021
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48. Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes

Author: Deelen, Joris, Evans, Daniel S., Arking, Dan E., Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K., Biggs, Mary L., van der Spek, Ashley, Atzmon, Gil, Ware, Erin B., Sarnowski, Chloé, Smith, Albert V., Seppälä, Ilkka, Cordell, Heather J., Dose, Janina, Amin, Najaf, Arnold, Alice M., Ayers, Kristin L., Barzilai, Nir, Becker, Elizabeth J., Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C., Cubaynes, Sarah, Cummings, Steven R., Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D., Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B., Huisman, Martijn, Hurme, Mikko A., Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon L. R., Kingston, Andrew, Kirkwood, Thomas B. L., Launer, Lenore J., Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B., Nie, Chao, Nohr, Ellen A., Orwoll, Eric S., Perls, Thomas T., Province, Michael A., Psaty, Bruce M., Raitakari, Olli T., Reinders, Marcel J. T., Robine, Jean-Marie, Rotter, Jerome I., Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild I. A., Taylor, Kent D., Uitterlinden, André G., van der Flier, Wiesje, van der Lee, Sven J., van Duijn, Cornelia M., van Heemst, Diana, Vaupel, James W., Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P., Lunetta, Kathryn L., Slagboom, P. Eline, and Murabito, Joanne M.
Published: 2021
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49. Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families

Author: Kuipers, Allison L., Wojczynski, Mary K., Barinas-Mitchell, Emma, Minster, Ryan L., Wang, Lihua, Feitosa, Mary F., Kulminski, Alexander, Thyagarajan, Bharat, Lee, Joseph H., Province, Michael A., Newman, Anne B., and Zmuda, Joseph M.
Published: 2019
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50. Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians 1 , 2

Author: Fretts, Amanda M, Follis, Jack L, Nettleton, Jennifer A, Lemaitre, Rozenn N, Ngwa, Julius S, Wojczynski, Mary K, Kalafati, Ioanna Panagiota, Varga, Tibor V, Frazier-Wood, Alexis C, Houston, Denise K, Lahti, Jari, Ericson, Ulrika, van den Hooven, Edith H, Mikkilä, Vera, Kiefte-de Jong, Jessica C, Mozaffarian, Dariush, Rice, Kenneth, Renström, Frida, North, Kari E, McKeown, Nicola M, Feitosa, Mary F, Kanoni, Stavroula, Smith, Caren E, Garcia, Melissa E, Tiainen, Anna-Maija, Sonestedt, Emily, Manichaikul, Ani, van Rooij, Frank JA, Dimitriou, Maria, Raitakari, Olli, Pankow, James S, Djoussé, Luc, Province, Michael A, Hu, Frank B, Lai, Chao-Qiang, Keller, Margaux F, Perälä, Mia-Maria, Rotter, Jerome I, Hofman, Albert, Graff, Misa, Kähönen, Mika, Mukamal, Kenneth, Johansson, Ingegerd, Ordovas, Jose M, Liu, Yongmei, Männistö, Satu, Uitterlinden, André G, Deloukas, Panos, Seppälä, Ilkka, Psaty, Bruce M, Cupples, L Adrienne, Borecki, Ingrid B, Franks, Paul W, Arnett, Donna K, Nalls, Mike A, Eriksson, Johan G, Orho-Melander, Marju, Franco, Oscar H, Lehtimäki, Terho, Dedoussis, George V, Meigs, James B, and Siscovick, David S
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Diabetes, Genetics, Aging, Cardiovascular, Nutrition, Metabolic and endocrine, Blood Glucose, Cohort Studies, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hyperglycemia, Hyperinsulinism, Insulin, Insulin Resistance, Insulin Secretion, Insulin-Secreting Cells, Meat, Meat Products, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, diet, gene–diet interaction, glucose, insulin, meat intake, meta-analysis, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract: BackgroundRecent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown.ObjectiveWe investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus.DesignFourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations.ResultsProcessed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance.ConclusionThe association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).
Published: 2015

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