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1. 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

2. Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, and Benito, Yolanda A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Alzheimer Disease Genetics Consortium, European Alzheimer’s Disease Initiative, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology, Genetics
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

3. 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

4. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, and Benito, Yolanda A

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Neurodegenerative, Dementia, Alzheimer's Disease, Aging, Prevention, Brain Disorders, Neurosciences, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Haplotypes, Humans, Immunity, Lipid Metabolism, Lipids, Male, tau Proteins, Alzheimer Disease Genetics Consortium (ADGC), European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Published
2019

5. 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

6. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

Author

Sims, Rebecca, van der Lee, Sven J, Naj, Adam C, Bellenguez, Céline, Badarinarayan, Nandini, Jakobsdottir, Johanna, Kunkle, Brian W, Boland, Anne, Raybould, Rachel, Bis, Joshua C, Martin, Eden R, Grenier-Boley, Benjamin, Heilmann-Heimbach, Stefanie, Chouraki, Vincent, Kuzma, Amanda B, Sleegers, Kristel, Vronskaya, Maria, Ruiz, Agustin, Graham, Robert R, Olaso, Robert, Hoffmann, Per, Grove, Megan L, Vardarajan, Badri N, Hiltunen, Mikko, Nöthen, Markus M, White, Charles C, Hamilton-Nelson, Kara L, Epelbaum, Jacques, Maier, Wolfgang, Choi, Seung-Hoan, Beecham, Gary W, Dulary, Cécile, Herms, Stefan, Smith, Albert V, Funk, Cory C, Derbois, Céline, Forstner, Andreas J, Ahmad, Shahzad, Li, Hongdong, Bacq, Delphine, Harold, Denise, Satizabal, Claudia L, Valladares, Otto, Squassina, Alessio, Thomas, Rhodri, Brody, Jennifer A, Qu, Liming, Sánchez-Juan, Pascual, Morgan, Taniesha, Wolters, Frank J, Zhao, Yi, Garcia, Florentino Sanchez, Denning, Nicola, Fornage, Myriam, Malamon, John, Naranjo, Maria Candida Deniz, Majounie, Elisa, Mosley, Thomas H, Dombroski, Beth, Wallon, David, Lupton, Michelle K, Dupuis, Josée, Whitehead, Patrice, Fratiglioni, Laura, Medway, Christopher, Jian, Xueqiu, Mukherjee, Shubhabrata, Keller, Lina, Brown, Kristelle, Lin, Honghuang, Cantwell, Laura B, Panza, Francesco, McGuinness, Bernadette, Moreno-Grau, Sonia, Burgess, Jeremy D, Solfrizzi, Vincenzo, Proitsi, Petra, Adams, Hieab H, Allen, Mariet, Seripa, Davide, Pastor, Pau, Cupples, L Adrienne, Price, Nathan D, Hannequin, Didier, Frank-García, Ana, Levy, Daniel, Chakrabarty, Paramita, Caffarra, Paolo, Giegling, Ina, Beiser, Alexa S, Giedraitis, Vilmantas, Hampel, Harald, Garcia, Melissa E, Wang, Xue, Lannfelt, Lars, Mecocci, Patrizia, Eiriksdottir, Gudny, Crane, Paul K, Pasquier, Florence, and Boccardi, Virginia

Subjects
ARUK Consortium, GERAD/PERADES, CHARGE, ADGC, EADI, Microglia, Humans, Alzheimer Disease, Genetic Predisposition to Disease, Adaptor Proteins, Signal Transducing, Membrane Glycoproteins, Receptors, Immunologic, Odds Ratio, Case-Control Studies, Gene Expression Profiling, Amino Acid Sequence, Sequence Homology, Amino Acid, Gene Frequency, Genotype, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Phospholipase C gamma, Immunity, Innate, Protein Interaction Maps, Exome, Neurodegenerative, Brain Disorders, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Alzheimer's Disease, Aging, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Published
2017

7. Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.

Author

Jakobsdottir, Johanna, van der Lee, Sven J, Bis, Joshua C, Chouraki, Vincent, Li-Kroeger, David, Yamamoto, Shinya, Grove, Megan L, Naj, Adam, Vronskaya, Maria, Salazar, Jose L, DeStefano, Anita L, Brody, Jennifer A, Smith, Albert V, Amin, Najaf, Sims, Rebecca, Ibrahim-Verbaas, Carla A, Choi, Seung-Hoan, Satizabal, Claudia L, Lopez, Oscar L, Beiser, Alexa, Ikram, M Arfan, Garcia, Melissa E, Hayward, Caroline, Varga, Tibor V, Ripatti, Samuli, Franks, Paul W, Hallmans, Göran, Rolandsson, Olov, Jansson, Jan-Håkon, Porteous, David J, Salomaa, Veikko, Eiriksdottir, Gudny, Rice, Kenneth M, Bellen, Hugo J, Levy, Daniel, Uitterlinden, Andre G, Emilsson, Valur, Rotter, Jerome I, Aspelund, Thor, Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, Alzheimer’s Disease Genetic Consortium, Genetic and Environmental Risk in Alzheimer’s Disease consortium, O'Donnell, Christopher J, Fitzpatrick, Annette L, Launer, Lenore J, Hofman, Albert, Wang, Li-San, Williams, Julie, Schellenberg, Gerard D, Boerwinkle, Eric, Psaty, Bruce M, Seshadri, Sudha, Shulman, Joshua M, Gudnason, Vilmundur, and van Duijn, Cornelia M

Subjects
Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, Alzheimer’s Disease Genetic Consortium, Genetic and Environmental Risk in Alzheimer’s Disease consortium, Animals, Humans, Drosophila melanogaster, Alzheimer Disease, Intracellular Signaling Peptides and Proteins, Amyloid beta-Protein Precursor, Apolipoproteins E, Tropomyosin, Drosophila Proteins, Membrane Proteins, Genomics, Age of Onset, Phenotype, Mutation, Alleles, Aged, European Continental Ancestry Group, Iceland, Female, Male, Receptors, Notch, Genome-Wide Association Study, Exome, Receptors, Notch, Genetics, Developmental Biology
Abstract

We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus

Published
2016

8. GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.

Author

Matteini, Amy M, Tanaka, Toshiko, Karasik, David, Atzmon, Gil, Chou, Wen-Chi, Eicher, John D, Johnson, Andrew D, Arnold, Alice M, Callisaya, Michele L, Davies, Gail, Evans, Daniel S, Holtfreter, Birte, Lohman, Kurt, Lunetta, Kathryn L, Mangino, Massimo, Smith, Albert V, Smith, Jennifer A, Teumer, Alexander, Yu, Lei, Arking, Dan E, Buchman, Aron S, Chibinik, Lori B, De Jager, Philip L, Evans, Denis A, Faul, Jessica D, Garcia, Melissa E, Gillham-Nasenya, Irina, Gudnason, Vilmundur, Hofman, Albert, Hsu, Yi-Hsiang, Ittermann, Till, Lahousse, Lies, Liewald, David C, Liu, Yongmei, Lopez, Lorna, Rivadeneira, Fernando, Rotter, Jerome I, Siggeirsdottir, Kristin, Starr, John M, Thomson, Russell, Tranah, Gregory J, Uitterlinden, André G, Völker, Uwe, Völzke, Henry, Weir, David R, Yaffe, Kristine, Zhao, Wei, Zhuang, Wei Vivian, Zmuda, Joseph M, Bennett, David A, Cummings, Steven R, Deary, Ian J, Ferrucci, Luigi, Harris, Tamara B, Kardia, Sharon LR, Kocher, Thomas, Kritchevsky, Stephen B, Psaty, Bruce M, Seshadri, Sudha, Spector, Timothy D, Srikanth, Velandai K, Windham, B Gwen, Zillikens, M Carola, Newman, Anne B, Walston, Jeremy D, Kiel, Douglas P, and Murabito, Joanne M

Subjects
Humans, Hand Strength, Cohort Studies, Reproducibility of Results, Chromatin Immunoprecipitation, Epigenesis, Genetic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Adult, Aged, Muscle Strength, Genome-Wide Association Study, Molecular Sequence Annotation, SNP, aging, genomewide association, meta-analysis, muscle strength, older adults, Epigenesis, Genetic, Polymorphism, Single Nucleotide, Developmental Biology, Medical and Health Sciences, Biological Sciences
Abstract

Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10(-8) ) and 39 suggestive (P-value< 5 × 10(-5) ) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10(-10) ). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.

Published
2016

9. Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits

Author

Pankratz, Nathan, Schick, Ursula M, Zhou, Yi, Zhou, Wei, Ahluwalia, Tarunveer Singh, Allende, Maria Laura, Auer, Paul L, Bork-Jensen, Jette, Brody, Jennifer A, Chen, Ming-Huei, Clavo, Vinna, Eicher, John D, Grarup, Niels, Hagedorn, Elliott J, Hu, Bella, Hunker, Kristina, Johnson, Andrew D, Leusink, Maarten, Lu, Yingchang, Lyytikainen, Leo-Pekka, Manichaikul, Ani, Marioni, Riccardo E, Nalls, Mike A, Pazoki, Raha, Smith, Albert Vernon, van Rooij, Frank JA, Yang, Min-Lee, Zhang, Xiaoling, Zhang, Yan, Asselbergs, Folkert W, Boerwinkle, Eric, Borecki, Ingrid B, Bottinger, Erwin P, Cushman, Mary, de Bakker, Paul IW, Deary, Ian J, Dong, Liguang, Feitosa, Mary F, Floyd, James S, Franceschini, Nora, Franco, Oscar H, Garcia, Melissa E, Grove, Megan L, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B, Hofman, Albert, Jackson, Rebecca D, Jia, Jia, Kahonen, Mika, Launer, Lenore J, Lehtimaki, Terho, Liewald, David C, Linneberg, Allan, Liu, Yongmei, Loos, Ruth JF, Nguyen, Vy M, Numans, Mattijs E, Pedersen, Oluf, Psaty, Bruce M, Raitakari, Olli T, Rich, Stephen S, Rivadeneira, Fernando, Di Sant, Amanda M Rosa, Rotter, Jerome I, Starr, John M, Taylor, Kent D, Thuesen, Betina Heinsbaek, Tracy, Russell P, Uitterlinden, Andre G, Wang, Jiansong, Wang, Judy, Dehghan, Abbas, Huo, Yong, Cupples, L Adrienne, Wilson, James G, Proia, Richard L, Zon, Leonard I, O'Donnell, Christopher J, Reiner, Alex P, and Ganesh, Santhi K

Subjects
Biological Sciences, Genetics, Prevention, Human Genome, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Animals, Erythrocyte Count, Erythrocytes, Ethnicity, Exome, Female, Genetic Loci, Genome-Wide Association Study, Hematocrit, Humans, Male, Mice, Quantitative Trait Loci, Receptors, Lysosphingolipid, Zebrafish, CHARGE Consortium Hematology Working Group, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Hematologic measures such as hematocrit and white blood cell (WBC) count are heritable and clinically relevant. We analyzed erythrocyte and WBC phenotypes in 52,531 individuals (37,775 of European ancestry, 11,589 African Americans, and 3,167 Hispanic Americans) from 16 population-based cohorts with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC count (MYB). The association of a rare missense variant in S1PR4 supports the role of sphingosine-1-phosphate signaling in leukocyte trafficking and circulating neutrophil counts. Loss-of-function experiments for S1pr4 in mouse and s1pr4 in zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury.

Published
2016

10. Atrial Fibrillation and Declining Physical Performance in Older Adults: The Health, Aging, and Body Composition Study.

Author

Magnani, Jared W, Wang, Na, Benjamin, Emelia J, Garcia, Melissa E, Bauer, Douglas C, Butler, Javed, Ellinor, Patrick T, Kritchevsky, Stephen, Marcus, Gregory M, Newman, Anne, Phillips, Caroline L, Sasai, Hiroyuki, Satterfield, Suzanne, Sullivan, Lisa M, Harris, Tamara B, and Health, Aging, and Body Composition Study

Subjects
Health, Aging, and Body Composition Study, Humans, Atrial Fibrillation, Electrocardiography, Disability Evaluation, Prevalence, Risk Assessment, Risk Factors, Follow-Up Studies, Prospective Studies, Motor Activity, Age Factors, Health Status, Body Composition, Aging, Time Factors, Aged, Aged, 80 and over, United States, Female, Male, aging, atrial fibrillation, epidemiology, medicare, physical exercise, Basic Behavioral and Social Science, Clinical Research, Cardiovascular, Behavioral and Social Science, Heart Disease, Prevention, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Medical Physiology, Cardiovascular System & Hematology
Abstract

BackgroundAge is the foremost risk factor for atrial fibrillation (AF), and AF has a rising prevalence in older adults. How AF may contribute to decline in physical performance in older adults has had limited investigation. We examined the associations of incident AF and 4-year interval declines in physical performance at ages 70, 74, 78, and 82 years in the Health, Aging, and Body Composition (Health ABC) Study.Methods and resultsHealth ABC is a prospective cohort of community-dwelling older adults (n=3075). The study conducted serial assessments of physical performance with the Health ABC physical performance battery (scored 0-4), grip strength, 2-minute walk distance, and 400-m walking time. Incident AF was identified from the Center for Medicare and Medicaid Services and related to 4-year interval decline in physical performance. After exclusions, the analysis included 2753 Health ABC participants (52% women, 41% black race). Participants with AF had a significantly greater 4-year physical performance battery decline than those without AF at age 70, 74, 78, and 82, with mean estimated decline ranging from -0.08 to -0.10 U (95% confidence interval, -0.18 to -0.01; P

Published
2016

11. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Author

Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Del Greco M, Fabiola, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton JN, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, and Savage, David B

Subjects
Adipose Tissue, Animals, Mice, Leptin, RNA, Messenger, Tissue Culture Techniques, Gene Expression Regulation, Male, Genome-Wide Association Study, Gene Knockdown Techniques, RNA, Messenger
Abstract

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P

Published
2016

12. 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

13. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Author

Day, Felix R, Ruth, Katherine S, Thompson, Deborah J, Lunetta, Kathryn L, Pervjakova, Natalia, Chasman, Daniel I, Stolk, Lisette, Finucane, Hilary K, Sulem, Patrick, Bulik-Sullivan, Brendan, Esko, Tõnu, Johnson, Andrew D, Elks, Cathy E, Franceschini, Nora, He, Chunyan, Altmaier, Elisabeth, Brody, Jennifer A, Franke, Lude L, Huffman, Jennifer E, Keller, Margaux F, McArdle, Patrick F, Nutile, Teresa, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M, Schick, Ursula M, Smith, Jennifer A, Teumer, Alexander, Traglia, Michela, Vuckovic, Dragana, Yao, Jie, Zhao, Wei, Albrecht, Eva, Amin, Najaf, Corre, Tanguy, Hottenga, Jouke-Jan, Mangino, Massimo, Smith, Albert V, Tanaka, Toshiko, Abecasis, Goncalo, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Arndt, Volker, Arnold, Alice M, Barbieri, Caterina, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bernstein, Leslie, Bielinski, Suzette J, Blomqvist, Carl, Boerwinkle, Eric, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Borresen-Dale, Anne-Lise, Boutin, Thibaud S, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Burwinkel, Barbara, Campbell, Archie, Campbell, Harry, Chanock, Stephen J, Chapman, J Ross, Chen, Yii-Der Ida, Chenevix-Trench, Georgia, Couch, Fergus J, Coviello, Andrea D, Cox, Angela, Czene, Kamila, Darabi, Hatef, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dunning, Alison M, Eicher, John D, Fasching, Peter A, Faul, Jessica D, Figueroa, Jonine, Flesch-Janys, Dieter, Gandin, Ilaria, Garcia, Melissa E, García-Closas, Montserrat, Giles, Graham G, Girotto, Giorgia G, Goldberg, Mark S, González-Neira, Anna, Goodarzi, Mark O, Grove, Megan L, Gudbjartsson, Daniel F, Guénel, Pascal, Guo, Xiuqing, Haiman, Christopher A, Hall, Per, and Hamann, Ute

Subjects
PRACTICAL consortium, kConFab Investigators, AOCS Investigators, Generation Scotland, EPIC-InterAct Consortium, LifeLines Cohort Study, Hypothalamus, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, Genomics, Age Factors, Signal Transduction, DNA Repair, Aging, Reproduction, Menopause, Genotype, Phenotype, Models, Genetic, Adult, Middle Aged, Female, Gene Regulatory Networks, Genetic Variation, Genome-Wide Association Study, Models, Genetic, Developmental Biology, Medical and Health Sciences, Biological Sciences
Abstract

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Published
2015

14. Plasma phospholipid fatty acids and fish-oil consumption in relation to osteoporotic fracture risk in older adults: the Age, Gene/Environment Susceptibility Study 2–4

Author

Harris, Tamara B, Song, Xiaoling, Reinders, Ilse, Lang, Thomas F, Garcia, Melissa E, Siggeirsdottir, Kristin, Sigurdsson, Sigurdur, Gudnason, Vilmundur, Eiriksdottir, Gudny, Sigurdsson, Gunnar, Steingrimsdottir, Laufey, Aspelund, Thor, Brouwer, Ingeborg A, and Murphy, Rachel A

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Osteoporosis, Clinical Research, Genetics, Prevention, Nutrition, Aging, Aged, Aged, 80 and over, Arachidonic Acid, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Fatty Acids, Omega-6, Female, Fish Oils, Follow-Up Studies, Humans, Male, Osteoporotic Fractures, Phospholipids, Proportional Hazards Models, Retrospective Studies, Risk Factors, Surveys and Questionnaires, fatty acids, fish oil, osteoporotic fracture, aging, omega-3, bone health, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

BackgroundPolyunsaturated fatty acids (PUFAs) may play a role in fracture, but studies have been largely confined to estimates of dietary intake.ObjectiveWe aimed to examine associations between fatty acids measured in late life and fish-oil consumption in early life, midlife, and late life with osteoporotic fracture risk.DesignOsteoporotic fractures were determined from medical records over 5-9 y of follow-up in men and women aged 66-96 y. Data were analyzed from 1438 participants including 898 participants who were randomly selected from the Age, Gene/Environment Susceptibility Study, which is an observational study, and 540 participants with incident fracture. Plasma phospholipid fatty acids were assessed by using gas chromatography. Fish-oil consumption was assessed by using validated questionnaires as never (referent), less than daily, or daily. HRs and 95% CIs adjusted for age, education, height, weight, diabetes, physical activity, and medications were estimated by using Cox regression.ResultsIn men, the highest tertile of PUFAs, n-3 (ω-3), and eicosapentaenoic acid were associated with decreased fracture risk [HRs (95% CIs): 0.60 (95% CI: 0.41, 0.89), 0.66 (0.45, 0.95), and 0.59 (0.41, 0.86), respectively]. In women, PUFAs tended to be inversely associated with fracture risk (P-trend = 0.06), but tertiles 2 and 3 were not independently associated with risk. Tertile 2 of n-6 and arachidonic acid was associated with fracture risk in women [HRs (95% CIs): 1.43 (1.10, 1.85) and 1.42 (1.09, 1.85), respectively]. Daily fish-oil consumption in late life was associated with lower fracture risk in men (HR: 0.64; 95% CI: 0.45, 0.91). Daily fish-oil consumption in midlife was associated with lower fracture risk in women (HR: 0.75; 95% CI: 0.58, 0.98).ConclusionsGreater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults, particularly in men. Critical time periods for n-3 fatty acid consumption may differ by sex.

Published
2015

15. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Locke, Adam E, Mägi, Reedik, Strawbridge, Rona J, Pers, Tune H, Fischer, Krista, Justice, Anne E, Workalemahu, Tsegaselassie, Wu, Joseph MW, Buchkovich, Martin L, Heard-Costa, Nancy L, Roman, Tamara S, Drong, Alexander W, Song, Ci, Gustafsson, Stefan, Day, Felix R, Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C, Scherag, André, Vedantam, Sailaja, Wood, Andrew R, Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Ehret, Georg B, Feitosa, Mary F, Goel, Anuj, Jackson, Anne U, Johnson, Toby, Kleber, Marcus E, Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V, Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B, Caspersen, Ida H, Clarke, Robert, Warwick Daw, E, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex SF, Eklund, Niina, Erdos, Michael R, Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S, Golay, Alain, Grallert, Harald, Grammer, Tanja B, Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J, Haller, Toomas, and Hallmans, Goran

Subjects
Genetics, Human Genome, Diabetes, Obesity, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Cardiovascular, Stroke, Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Fat Distribution, Body Mass Index, Epigenesis, Genetic, Europe, Female, Genome, Human, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Male, Models, Biological, Neovascularization, Physiologic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Sex Characteristics, Transcription, Genetic, Waist-Hip Ratio, ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, GLGC, ICBP, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, General Science & Technology
Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P

Published
2015

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

Author

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

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

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

Published
2015

17. GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.

Author

Broer, Linda, Buchman, Aron S, Deelen, Joris, Evans, Daniel S, Faul, Jessica D, Lunetta, Kathryn L, Sebastiani, Paola, Smith, Jennifer A, Smith, Albert V, Tanaka, Toshiko, Yu, Lei, Arnold, Alice M, Aspelund, Thor, Benjamin, Emelia J, De Jager, Philip L, Eirkisdottir, Gudny, Evans, Denis A, Garcia, Melissa E, Hofman, Albert, Kaplan, Robert C, Kardia, Sharon LR, Kiel, Douglas P, Oostra, Ben A, Orwoll, Eric S, Parimi, Neeta, Psaty, Bruce M, Rivadeneira, Fernando, Rotter, Jerome I, Seshadri, Sudha, Singleton, Andrew, Tiemeier, Henning, Uitterlinden, André G, Zhao, Wei, Bandinelli, Stefania, Bennett, David A, Ferrucci, Luigi, Gudnason, Vilmundur, Harris, Tamara B, Karasik, David, Launer, Lenore J, Perls, Thomas T, Slagboom, P Eline, Tranah, Gregory J, Weir, David R, Newman, Anne B, van Duijn, Cornelia M, and Murabito, Joanne M

Subjects
Humans, Apolipoproteins E, Cell Adhesion Molecules, Receptors, Kainic Acid, Cohort Studies, Longevity, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Female, Male, Forkhead Transcription Factors, Genome-Wide Association Study, Forkhead Box Protein O3, APOE., FOXO3, GWAS, APOE, Receptors, Kainic Acid, Polymorphism, Single Nucleotide, and over, Gerontology, Clinical Sciences
Abstract

BackgroundThe genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.MethodsWe conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.ResultsIn our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).ConclusionsWe did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

Published
2015

18. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

Author

Perry, John RB, Day, Felix, Elks, Cathy E, Sulem, Patrick, Thompson, Deborah J, Ferreira, Teresa, He, Chunyan, Chasman, Daniel I, Esko, Tõnu, Thorleifsson, Gudmar, Albrecht, Eva, Ang, Wei Q, Corre, Tanguy, Cousminer, Diana L, Feenstra, Bjarke, Franceschini, Nora, Ganna, Andrea, Johnson, Andrew D, Kjellqvist, Sanela, Lunetta, Kathryn L, McMahon, George, Nolte, Ilja M, Paternoster, Lavinia, Porcu, Eleonora, Smith, Albert V, Stolk, Lisette, Teumer, Alexander, Tšernikova, Natalia, Tikkanen, Emmi, Ulivi, Sheila, Wagner, Erin K, Amin, Najaf, Bierut, Laura J, Byrne, Enda M, Hottenga, Jouke-Jan, Koller, Daniel L, Mangino, Massimo, Pers, Tune H, Yerges-Armstrong, Laura M, Hua Zhao, Jing, Andrulis, Irene L, Anton-Culver, Hoda, Atsma, Femke, Bandinelli, Stefania, Beckmann, Matthias W, Benitez, Javier, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Buring, Julie E, Chang-Claude, Jenny, Chanock, Stephen, Chen, Jinhui, Chenevix-Trench, Georgia, Collée, J Margriet, Couch, Fergus J, Couper, David, Coviello, Andrea D, Cox, Angela, Czene, Kamila, D’adamo, Adamo Pio, Davey Smith, George, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dieffenbach, Aida K, Dunning, Alison M, Eiriksdottir, Gudny, Eriksson, Johan G, Fasching, Peter A, Ferrucci, Luigi, Flesch-Janys, Dieter, Flyger, Henrik, Foroud, Tatiana, Franke, Lude, Garcia, Melissa E, García-Closas, Montserrat, Geller, Frank, de Geus, Eco EJ, Giles, Graham G, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Guénel, Pascal, Guo, Suiqun, Hall, Per, Hamann, Ute, Haring, Robin, Hartman, Catharina A, Heath, Andrew C, Hofman, Albert, Hooning, Maartje J, Hopper, John L, Hu, Frank B, Hunter, David J, Karasik, David, and Kiel, Douglas P

Subjects
Paediatrics, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Contraception/Reproduction, Pediatric, Biotechnology, Human Genome, Clinical Research, Adolescent, Age Factors, Alleles, Body Mass Index, Breast Neoplasms, Calcium-Binding Proteins, Cardiovascular Diseases, Child, Diabetes Mellitus, Type 2, Europe, Female, Genetic Loci, Genome-Wide Association Study, Genomic Imprinting, Humans, Hypothalamo-Hypophyseal System, Intercellular Signaling Peptides and Proteins, Male, Membrane Proteins, Menarche, Obesity, Ovary, Parents, Polymorphism, Single Nucleotide, Potassium Channels, Tandem Pore Domain, Proteins, Quantitative Trait Loci, Receptors, GABA-B, Receptors, Retinoic Acid, Ribonucleoproteins, Ubiquitin-Protein Ligases, Australian Ovarian Cancer Study, GENICA Network, kConFab, LifeLines Cohort Study, InterAct Consortium, Early Growth Genetics (EGG) Consortium, General Science & Technology
Abstract

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P

Published
2014

19. Meta-analysis of loci associated with age at natural menopause in African-American women

Author

Chen, Christina TL, Liu, Ching-Ti, Chen, Gary K, Andrews, Jeanette S, Arnold, Alice M, Dreyfus, Jill, Franceschini, Nora, Garcia, Melissa E, Kerr, Kathleen F, Li, Guo, Lohman, Kurt K, Musani, Solomon K, Nalls, Michael A, Raffel, Leslie J, Smith, Jennifer, Ambrosone, Christine B, Bandera, Elisa V, Bernstein, Leslie, Britton, Angela, Brzyski, Robert G, Cappola, Anne, Carlson, Christopher S, Couper, David, Deming, Sandra L, Goodarzi, Mark O, Heiss, Gerardo, John, Esther M, Lu, Xiaoning, Le Marchand, Loic, Marciante, Kristin, Mcknight, Barbara, Millikan, Robert, Nock, Nora L, Olshan, Andrew F, Press, Michael F, Vaiyda, Dhananjay, Woods, Nancy F, Taylor, Herman A, Zhao, Wei, Zheng, Wei, Evans, Michele K, Harris, Tamara B, Henderson, Brian E, Kardia, Sharon LR, Kooperberg, Charles, Liu, Yongmei, Mosley, Thomas H, Psaty, Bruce, Wellons, Melissa, Windham, Beverly G, Zonderman, Alan B, Cupples, L Adrienne, Demerath, Ellen W, Haiman, Christopher, Murabito, Joanne M, and Rajkovic, Aleksandar

Subjects
Contraception/Reproduction, Estrogen, Genetics, Human Genome, Aging, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Black or African American, Age Factors, Chromosomes, Human, Female, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Menopause, United States, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.

Published
2014

20. Comparison Between Southern Blots and qPCR Analysis of Leukocyte Telomere Length in the Health ABC Study

Author

Elbers, Clara C, Garcia, Melissa E, Kimura, Masayuki, Cummings, Steven R, Nalls, Mike A, Newman, Anne B, Park, Vicki, Sanders, Jason L, Tranah, Gregory J, Tishkoff, Sarah A, Harris, Tamara B, and Aviv, Abraham

Subjects
Aging, Black or African American, Aged, Blotting, Southern, Body Composition, Female, Humans, Leukocytes, Male, Real-Time Polymerase Chain Reaction, Telomere, White People, Leukocyte telomere length, Quantitative PCR, Southern blots., Clinical Sciences, Gerontology
Abstract

Only a few studies, primarily limited to small samples, have examined the relationship between leukocyte telomere length (LTL) data generated by Southern blots, expressed in kilobases, versus quantitative PCR data, expressed in the telomere product/a single gene product (T/S). In the present study, we compared LTL data generated by the two methods in 681 elderly participants (50% African Americans, 50% of European origin, 49.2% women, mean age 73.7±2.9 years) in the Health Aging and Body Composition Study. The correlation between the data generated by the two methods was modest (R (2) = .27). Both methods captured the age effect on LTL and the longer LTL in women than in men. However, only the Southern blot method showed a significantly longer LTL in African Americans than in European decent individuals, which might be attributed to the larger measurement error of the quantitative PCR-based method than the Southern blots.

Published
2014

21. Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations

Author

Franceschini, Nora, Fox, Ervin, Zhang, Zhaogong, Edwards, Todd L, Nalls, Michael A, Sung, Yun Ju, Tayo, Bamidele O, Sun, Yan V, Gottesman, Omri, Adeyemo, Adebawole, Johnson, Andrew D, Young, J Hunter, Rice, Ken, Duan, Qing, Chen, Fang, Li, Yun, Tang, Hua, Fornage, Myriam, Keene, Keith L, Andrews, Jeanette S, Smith, Jennifer A, Faul, Jessica D, Guangfa, Zhang, Guo, Wei, Liu, Yu, Murray, Sarah S, Musani, Solomon K, Srinivasan, Sathanur, Edwards, Digna R Velez, Wang, Heming, Becker, Lewis C, Bovet, Pascal, Bochud, Murielle, Broeckel, Ulrich, Burnier, Michel, Carty, Cara, Chasman, Daniel I, Ehret, Georg, Chen, Wei-Min, Chen, Guanjie, Chen, Wei, Ding, Jingzhong, Dreisbach, Albert W, Evans, Michele K, Guo, Xiuqing, Garcia, Melissa E, Jensen, Rich, Keller, Margaux F, Lettre, Guillaume, Lotay, Vaneet, Martin, Lisa W, Moore, Jason H, Morrison, Alanna C, Mosley, Thomas H, Ogunniyi, Adesola, Palmas, Walter, Papanicolaou, George, Penman, Alan, Polak, Joseph F, Ridker, Paul M, Salako, Babatunde, Singleton, Andrew B, Shriner, Daniel, Taylor, Kent D, Vasan, Ramachandran, Wiggins, Kerri, Williams, Scott M, Yanek, Lisa R, Zhao, Wei, Zonderman, Alan B, Becker, Diane M, Berenson, Gerald, Boerwinkle, Eric, Bottinger, Erwin, Cushman, Mary, Eaton, Charles, Nyberg, Fredrik, Heiss, Gerardo, Hirschhron, Joel N, Howard, Virginia J, Karczewsk, Konrad J, Lanktree, Matthew B, Liu, Kiang, Liu, Yongmei, Loos, Ruth, Margolis, Karen, Snyder, Michael, Consortium, the Asian Genetic Epidemiology Network, Go, Min Jin, Kim, Young Jin, Lee, Jong-Young, Jeon, Jae-Pil, Kim, Sung Soo, Han, Bok-Ghee, Cho, Yoon Shin, Sim, Xueling, Tay, Wan Ting, Ong, Rick Twee Hee, Seielstad, Mark, and Liu, Jian Jun

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Cardiovascular, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Africa, Black People, Blood Pressure, Cohort Studies, Databases, Genetic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Reproducibility of Results, Asian Genetic Epidemiology Network Consortium, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

Published
2013

22. Electrocardiographic PR Interval and Adverse Outcomes in Older Adults

Author

Magnani, Jared W, Wang, Na, Nelson, Kerrie P, Connelly, Stephanie, Deo, Rajat, Rodondi, Nicolas, Schelbert, Erik B, Garcia, Melissa E, Phillips, Caroline L, Shlipak, Michael G, Harris, Tamara B, Ellinor, Patrick T, and Benjamin, Emelia J

Subjects
Biomedical and Clinical Sciences, Medical Physiology, Cardiovascular Medicine and Haematology, Clinical Sciences, Heart Disease, Cardiovascular, Aging, Clinical Research, Good Health and Well Being, African Americans, Age Factors, Aged, Atrial Fibrillation, Electrocardiography, Female, Heart Failure, Heart Rate, Humans, Linear Models, Longitudinal Studies, Male, Multivariate Analysis, Odds Ratio, Pennsylvania, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Tennessee, Time Factors, Whites, atrial fibrillation, ECG, epidemiology, heart failure, risk factors, Health, Aging, and Body Composition Study, White People, Black or African American, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Medical physiology
Abstract

BackgroundThe electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults.Methods and resultsThe Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02-1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04-1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11-1.93). PR interval was not associated with increased all-cause mortality.ConclusionsWe identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.

Published
2013

23. Adverse Oral Health and Cognitive Decline: The Health, Aging and Body Composition Study

Author

Stewart, Robert, Weyant, Robert J, Garcia, Melissa E, Harris, Tamara, Launer, Lenore J, Satterfield, Suzanne, Simonsick, Eleanor M, Yaffe, Kristine, and Newman, Anne B

Subjects
Dental/Oral and Craniofacial Disease, Brain Disorders, Behavioral and Social Science, Aging, Acquired Cognitive Impairment, Mental Health, Prevention, Clinical Research, Dementia, Mental health, Good Health and Well Being, Aged, Body Composition, Cognition Disorders, Female, Humans, Male, Neuropsychological Tests, Oral Health, Prospective Studies, Risk Factors, cognitive decline, cognitive impairment, periodontitis, periodontal disease, gingivitis, Medical and Health Sciences, Geriatrics
Abstract

ObjectivesTo investigate the relationship between periodontal disease and cognitive decline.DesignAnalysis of a prospective cohort study.SettingThe Health, Aging and Body Composition (Health ABC) Study.ParticipantsOne thousand fifty-three participants who were administered the Modified Mini-Mental State Examination (3MS) at Year 1 (baseline) and Year 3 and had participated in a comprehensive periodontal examination at Year 2.MeasurementsThe prospective association between a range of oral health parameters and cognitive function was examined. Decline in 3MS score from Year 3 to 5 was investigated in 947 (89.9%) participants. Covariates included age, sex, education, race, cardiovascular disease and risk, and depressive symptoms.ResultsMost indicators of adverse oral health at Year 2 were associated with cognitive impairment based on averaged 3MS scores less than 80 for Years 1 and 3, but education and race substantially confounded these associations. Higher gingival index, a measure of gingival inflammation, at Year 2 remained independently associated with this definition of cognitive impairment and, in fully adjusted analyses, was also an independent predictor of a more-than-5-point cognitive decline from Year 3 to 5.ConclusionPeriodontitis may be a risk factor for cognitive decline. Gingivitis is reversible, and periodontitis to some degree is preventable and controllable when manifest. Therefore, further research is needed to clarify potential underlying mechanisms and oral health interventions that might ameliorate cognitive decline.

Published
2013

24. Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels

Author

Qi, Qibin, Menzaghi, Claudia, Smith, Shelly, Liang, Liming, de Rekeneire, Nathalie, Garcia, Melissa E, Lohman, Kurt K, Miljkovic, Iva, Strotmeyer, Elsa S, Cummings, Steve R, Kanaya, Alka M, Tylavsky, Frances A, Satterfield, Suzanne, Ding, Jingzhong, Rimm, Eric B, Trischitta, Vincenzo, Hu, Frank B, Liu, Yongmei, and Qi, Lu

Subjects
Clinical Research, Aging, Cardiovascular, Prevention, Heart Disease, Human Genome, Genetics, Diabetes, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Female, Gene Expression, Genome-Wide Association Study, Humans, Insulin Resistance, Membrane Proteins, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Resistin, Sulfotransferases, White People, zeta-Crystallins, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses' Health Study (n = 1590) and the Health, Aging and Body Composition Study (n = 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n = 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P = 6.37 × 10(-12)) and SNP rs13144478 (P = 6.19 × 10(-18)), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P = 3.68 × 10(-7)). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P = 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio = 1.18 (95% CI, 1.03-1.34); P = 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease.

Published
2012

25. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

Author

Speliotes, Elizabeth K, Yerges-Armstrong, Laura M, Wu, Jun, Hernaez, Ruben, Kim, Lauren J, Palmer, Cameron D, Gudnason, Vilmundur, Eiriksdottir, Gudny, Garcia, Melissa E, Launer, Lenore J, Nalls, Michael A, Clark, Jeanne M, Mitchell, Braxton D, Shuldiner, Alan R, Butler, Johannah L, Tomas, Marta, Hoffmann, Udo, Hwang, Shih-Jen, Massaro, Joseph M, O'Donnell, Christopher J, Sahani, Dushyant V, Salomaa, Veikko, Schadt, Eric E, Schwartz, Stephen M, Siscovick, David S, NASH CRN, GIANT Consortium, MAGIC Investigators, Voight, Benjamin F, Carr, J Jeffrey, Feitosa, Mary F, Harris, Tamara B, Fox, Caroline S, Smith, Albert V, Kao, WH Linda, Hirschhorn, Joel N, Borecki, Ingrid B, and GOLD Consortium

Subjects
NASH CRN, GIANT Consortium, MAGIC Investigators, GOLD Consortium, Humans, Fatty Liver, Insulin, Lipase, Blood Glucose, Adaptor Proteins, Signal Transducing, Lectins, C-Type, Membrane Proteins, Nerve Tissue Proteins, Tomography, X-Ray Computed, Case-Control Studies, Cohort Studies, Mutation, Missense, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Adult, Aged, Aged, 80 and over, Middle Aged, Male, Genome-Wide Association Study, Chondroitin Sulfate Proteoglycans, Non-alcoholic Fatty Liver Disease, Prevention, Human Genome, Digestive Diseases, Liver Disease, Hepatitis, Chronic Liver Disease and Cirrhosis, Genetics, Clinical Research, 2.1 Biological and endogenous factors, Developmental Biology
Abstract

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p

Published
2011

26. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author

Chauhan, Ganesh, Adams, Hieab H.H., Satizabal, Claudia L., Bis, Joshua C., Teumer, Alexander, Sargurupremraj, Muralidharan, Hofer, Edith, Trompet, Stella, Hilal, Saima, Smith, Albert Vernon, Jian, Xueqiu, Malik, Rainer, Traylor, Matthew, Pulit, Sara L., Amouyel, Philippe, Mazoyer, Bernard, Zhu, Yi-Cheng, Kaffashian, Sara, Schilling, Sabrina, Beecham, Gary W., Montine, Thomas J., Schellenberg, Gerard D., Kjartansson, Olafur, Guðnason, Vilmundur, Knopman, David S., Griswold, Michael E., Windham, B. Gwen, Gottesman, Rebecca F., Mosley, Thomas H., Schmidt, Reinhold, Saba, Yasaman, Schmidt, Helena, Takeuchi, Fumihiko, Yamaguchi, Shuhei, Nabika, Toru, Kato, Norihiro, Rajan, Kumar B., Aggarwal, Neelum T., De Jager, Philip L., Evans, Denis A., Psaty, Bruce M., Rotter, Jerome I., Rice, Kenneth, Lopez, Oscar L., Liao, Jiemin, Chen, Christopher, Cheng, Ching-Yu, Wong, Tien Y., Ikram, Mohammad K., van der Lee, Sven J., Amin, Najaf, Chouraki, Vincent, DeStefano, Anita L., Aparicio, Hugo J., Romero, Jose R., Maillard, Pauline, DeCarli, Charles, Wardlaw, Joanna M., Hernández, Maria del C. Valdés, Luciano, Michelle, Liewald, David, Deary, Ian J., Starr, John M., Bastin, Mark E., Muñoz Maniega, Susana, Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, Uh, Hae-Won, Lemmens, Robin, Brodaty, Henry, Wright, Margaret J., Ames, David, Boncoraglio, Giorgio B., Hopewell, Jemma C., Beecham, Ashley H., Blanton, Susan H., Wright, Clinton B., Sacco, Ralph L., Wen, Wei, Thalamuthu, Anbupalam, Armstrong, Nicola J., Chong, Elizabeth, Schofield, Peter R., Kwok, John B., van der Grond, Jeroen, Stott, David J., Ford, Ian, Jukema, J. Wouter, Vernooij, Meike W., Hofman, Albert, Uitterlinden, André G., van der Lugt, Aad, Wittfeld, Katharina, Grabe, Hans J., Hosten, Norbert, von Sarnowski, Bettina, Völker, Uwe, Levi, Christopher, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie L.M., Rosand, Jonathan, Woo, Daniel, Cole, John W., Meschia, James F., Slowik, Agnieszka, Thijs, Vincent, Lindgren, Arne, Melander, Olle, Grewal, Raji P., Rundek, Tatjana, Rexrode, Kathy, Rothwell, Peter M., Arnett, Donna K., Jern, Christina, Johnson, Julie A., Benavente, Oscar R., Wasssertheil-Smoller, Sylvia, Lee, Jin-Moo, Wong, Quenna, Mitchell, Braxton D., Rich, Stephen S., McArdle, Patrick F., Geerlings, Mirjam I., van der Graaf, Yolanda, de Bakker, Paul I.W., Asselbergs, Folkert W., Srikanth, Velandai, Thomson, Russell, McWhirter, Rebekah, Moran, Chris, Callisaya, Michele, Phan, Thanh, Rutten-Jacobs, Loes C.A., Bevan, Steve, Tzourio, Christophe, Mather, Karen A., Sachdev, Perminder S., van Duijn, Cornelia M., Worrall, Bradford B., Dichgans, Martin, Kittner, Steven J., Markus, Hugh S., Ikram, Mohammad A., Fornage, Myriam, Launer, Lenore J., Seshadri, Sudha, Longstreth, W.T., Jr, Debette, Stéphanie, Almgren, Peter, Anderson, Christopher D., Arnett, Donna K., Attia, John, Ay, Hakan, Benavente, Oscar R., Bevan, Steve, Brown, Robert D., Bustamante, Mariana, Cheng, Yu-Ching, Cole, John W., Cotlarciuc, Ioana, Cruchaga, Carlos, de Bakker, Paul IW., Delavaran, Hossein, Dichgans, Martin, Engström, Gunnar, Fornage, Myriam, Grewal, Raji P., Heitsch, Laura, Holliday, Elizabeth, Ibanez, Laure, Ilinca, Andreea, Irvin, Marguerite R., Jackson, Rebecca D., Jern, Christina, Jimenez-Conde, Jordi, Johnson, Julie A., Jood, Katarina, Kissela, Brett M., Kittner, Steven J., Kleindorfer, Dawn O., Labovitz, Daniel, Laurie, Cathy C., Lee, Jin-Moo, Lemmens, Robin, Levi, Christopher, Li, Linxin, Lindgren, Arne G., Maguire, Jane, Markus, Hugh S., McArdle, Patrick F., Melander, Olle, Meschia, James F., Mitchell, Braxton D., Müller-Nurasyid, Martina, Norrving, Bo, Peddareddygari, Leema Reddy, Pera, Joanna, Pulit, Sara L., Rexrode, Kathryn, Ribasés, Marta, Roquer, Jaume, Rost, Natalia S., Rothwell, Peter M., Rundek, Tatjana, Sacco, Ralph L., Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Soriano-Tárraga, Carolina, Stanne, Tara, Stauch, Konstantin, Stine, O C., Sudlow, Cathie LM., Thijs, Vincent N.S., Wasssertheil-Smoller, Sylvia, Weir, David, Williams, Stephen R., Wong, Quenna, Woo, Daniel, Worrall, Bradford B., Xu, Huichun, Seshadri, Sudha, Hyacinth, Hyacinth I, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Hansen, Bjorn, Norrving, Bo, Rosand, Jonathan, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Sacco, Ralph, Sharma, Pankaj, Chung, Jong-Won, Kim, Gyeong-Moon, Lubitz, Steven, Bourcier, Romain, Howson, Joanna, Granata, Alessandra, Drazyk, Anna, Markus, Hugh, Wardlaw, Joanna, Mitchell, Braxton, Cole, John, Hopewell, Jemma, Walters, Robin, Turnbull, Iain, Worrall, Bradford, Bis, Josh, Reiner, Alex, Dhar, Raj, Heitsch, Laura, Lee, Jin-Moo, Prasad, Kameshwar, Sarnowski, Chloé, Aparicio, Hugo Javier, Yang, Qiong, Chasman, Daniel, Rexrode, Kathryn, Phuah, Chia-Ling, Liu, Guiyou, Elkind, Mitchell, Lange, Leslie, Rost, Natalia, James, Michael, Stewart, Jill, Vojinovic, Dina, Thijs, Vincent, Parati, Eugenio, Boncoraglio, Giorgio, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Grond-Ginsbach, Caspar, Strbian, Daniel, Tomppo, Liisa, Sallinen, Hanne, Pfeiffer, Dorothea, Torres, Nuria, Barboza, Miguel, Laarman, Melanie, Carriero, Roberta, Holliday, Elizabeth, Jimenez-Conde, Jordi, Soriano, Carolina, Gill, Dipender, Debette, Stephanie, Mishra, Aniket, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Jood, Katarina, Tatlisumak, Turgut, Holmegaard, Lukas, Yue, Suo, bersano, Anna, Pera, Joanna, Slowik, Agnieszka, Levi, Christopher, Schlicht, Kristina, Lemmens, Robin, Ninomiya, Toshiharu, Oberstein, Saskia Lesnik, Lee, Tsong-Hai, Malik, Rainer, Dichgans, Martin, Lindgren, Arne, Wasselius, Johan, Drake, Mattias, Melander, Olle, Stenman, Martin, Ilinca, Andreea, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Ay, Hakan, Wu, Ona, Schirmer, Markus, Cramer, Steve, Golland, Polina, Brown, Robert, Meschia, James, Ross, Owen A., Pare, Guillaume, Chong, Mike, Rundek, Tatjana, Gwinn, Katrina, Chen, Christopher, Koenig, Jim, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Kamatani, Yoichiro, Kubo, Michiaki, Okada, Yukinori, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Xu, Huichun, Tan, Eng King, Frid, Petrea, Lee, Chaeyoung, Tregouet, David, Leung, Thomas, Choy, Richard, Jern, Christina, Loo, Keat Wei, Rinkel, Gabriel, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Montaner, Joan, Kim, Helen, Owolabi, Mayowa, Sofat, Reecha, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, Pulit, Sara L., van der Laan, Sander W., Irvin, Ryan, Sargurupremraj, Murali, Pezzini, Alessandro, Abd-Allah, Foad, Liebeskind, David, Traylor, Matthew, Tan, Rhea, Danesh, John, Rutten-Jacobs, Loes, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Woo, Daniel, Sudlow, Cathie, Rannikmae, Kristiina, McDonough, Caitrin Wheeler, van Agtmael, Tom, Walters, Matthew, Söderholm, Martin, Lorentzen, Erik, Olsson, Sandra, Stanne, Tara, Olsson, Martina, Akinyemi, Rufus, Cotlatciuc, Ioana, McArdle, Patrick, Dave, Tushar, Kittner, Steven, Attia, John, Faber, James E, Millwood, Iona, Márquez, Elsa Valdés, Mancuso, Michelangelo, Vibo, Riina, Korv, Janika, Maguire, Jane, Fornage, Myriam, Majersik, Jennifer, DeHavenon, Adam, Alexander, Matthew, Sale, Michele, Southerland, Andrew, Owens, Debra, Psaty, Bruce, Longstreth, W. T., Jr, Wolfe, Stacey Quintero, Langefeld, Carl, Cruchaga, Carlos, Konrad, Jan, Sheth, Kevin, Falcone, Guido, Donahue, Kathleen, Simpkins, Alexis N, Liang Byorn, Tan Wei, Chan, Bernard, Clatworthy, Phil, Florez, Jose, Harshfield, Eric, Hozawa, Atsushi, Hsu, Chung, Hu, Chaur-Jong, Ibanez, Laure, Ihara, Masafumi, Lange, Marcos, Lee, Soo Ji, Lee, I-Hui, Musolino, Patricia, Nakatomi, Hirofumi, Park, Kwang-Yeol, Rich, Stephen S, Riley, Chris, Sung, Joohon, Suzuki, Hideaki, Vo, Katie, Washida, Kazuo, Ibenez, Laura Garcia, Slowik, Agnieszka, Hofman, Albert, Algra, Ale, Reiner, Alex P, Doney, Alexander S F, Gschwendtner, Andreas, Ilinca, Andreea, Giese, Anne-Katrin, Lindgren, Arne, Vicente, Astrid M, Norrving, Bo, Nordestgaard, Børge G, Mitchell, Braxton D, Worrall, Bradford B, Psaty, Bruce M, Carty, Cara L, Sudlow, Cathie, Anderson, Christopher D, Levi, Christopher, Satizabal, Claudia L, Palmer, Colin N A, Gamble, Dale M, Woo, Daniel, Saleheen, Danish, Ringelstein, E Bernd, Valdimarsson, Einar, Holliday, Elizabeth, Davies, Gail, Chauhan, Ganesh, Pasterkamp, Gerard, Boncoraglio, Giorgio, Kuhlenbäumer, Gregor, Thorleifsson, Gudmar, Falcone, Guido J, Pare, Guillame, Schmidt, Helena, Delavaran, Hossein, Markus, Hugh S, Aparicio, Hugo J, Deary, Ian, Cotlarciuc, Ioana, Fernandez-Cadenas, Israel, Meschia, James, Hopewell, Jemma C, Liu, Jingmin, Montaner, Joan, Pera, Joanna, Cole, John, Attia, John R, Rosand, Jonathan, Ferro, Jose M, Bis, Joshua, Furie, Karen, Stefansson, Kari, Berger, Klaus, Kostulas, Konstantinos, Rannikmae, Kristina, Ikram, M Arfan, Benn, Marianne, Dichgans, Martin, Farrall, Martin, Pandolfo, Massimo, Traylor, Matthew, Walters, Matthew, Sale, Michele, Nalls, Mike, Fornage, Myriam, van Zuydam, Natalie R, Sharma, Pankaj, Abrantes, Patricia, de Bakker, Paul IW, Higgins, Peter, Lichtner, Peter, Rothwell, Peter M, Amouyel, Philippe, Yang, Qiong, Malik, Rainer, Schmidt, Reinhold, Clarke, Robert, Lemmens, Robin, van der Laan, Sander W, Pulit, Sara L, Abboud, Sherine, Oliveira, Sofia A, Gretarsdottir, Solveig, Debette, Stephanie, Williams, Stephen R, Bevan, Steve, Kittner, Steven J, Seshadri, Sudha, Mosley, Thomas, Battey, Thomas WK, Tatlisumak, Turgut, Thorsteinsdottir, Unnur, Thijs, Vincent NS, Longstreth, W T, Zhao, Wei, Chen, Wei-Min, Cheng, Yu-Ching, Albert, Marilyn S., Albin, Roger L., Apostolova, Liana G., Arnold, Steven E., Asthana, Sanjay, Atwood, Craig S., Baldwin, Clinton T., Barmada, M. Michael, Barnes, Lisa L., Barral, Sandra, Beach, Thomas G., Becker, James T., Beecham, Gary W., Beekly, Duane, Bennett, David A., Bigio, Eileen H., Bird, Thomas D., Blacker, Deborah, Boeve, Bradley F., Boxer, Adam, Burke, James R., Burns, Jeffrey M., Buxbaum, Joseph D., Byrd, Goldie S., Cai, Guiqing, Cairns, Nigel J., Cantwell, Laura B., Cao, Chuanhai, Carlsson, Cynthia M., Carney, Regina M., Carrasquillo, Minerva M., Carroll, Steven L., Chui, Helena C., Clark, David G., Cribbs, David H., Crocco, Elizabeth A., Cruchaga, Carlos, De Jager, Philip L., DeCarli, Charles, Demirci, F. Yesim, Dick, Malcolm, Dickson, Dennis W., Duara, Ranjan, Ertekin-Taner, Nilufer, Evans, Denis A., Faber, Kelley M., Fallin, M. Daniele, Fallon, Kenneth B., Fardo, David W., Farlow, Martin R., Farrer, Lindsay A., Ferris, Steven, Foroud, Tatiana M., Frosch, Matthew P., Galasko, Douglas R., Gearing, Marla, Geschwind, Daniel H., Ghetti, Bernardino, Gilbert, John R., Go, Rodney C.P., Goate, Alison M., Graff-Radford, Neill R., Green, Robert C., Griffith, Patrick, Growdon, John H., Haines, Jonathan L., Hakonarson, Hakon, Hamilton, Ronald L., Hamilton-Nelson, Kara L., Haroutunian, Vahram, Harrell, Lindy E., Honig, Lawrence S., Huebinger, Ryan M., Hulette, Christine M., Hyman, Bradley T., Jicha, Gregory A., Jin, Lee-Way, Jun, Gyungah, Kamboh, M. Ilyas, Karydas, Anna, Kauwe, John S.K., Kaye, Jeffrey A., Kim, Ronald, Kowall, Neil W., Kramer, Joel H., Kukull, Walter A., Kunkle, Brian W., LaFerla, Frank M., Lah, James J., Lang-Walker, Rosalyn, Larson, Eric B., Leverenz, James B., Levey, Allan I., Li, Ge, Lieberman, Andrew P., Logue, Mark W., Lopez, Oscar L., Lunetta, Kathryn L., Lyketsos, Constantine G., Mack, Wendy J., Manly, Jennifer J., Marson, Daniel C., Martin, Eden R., Martiniuk, Frank, Mash, Deborah C., Masliah, Eliezer, Mayeux, Richard, McKee, Ann C., Mesulam, Marsel, Miller, Bruce L., Miller, Carol A., Miller, Joshua W., Montine, Thomas J., Morris, John C., Murrell, Jill R., Naj, Adam C., Obisesan, Thomas O., Olichney, John M., Pankratz, Vernon S., Parisi, Joseph E., Partch, Amanda, Paulson, Henry L., Pericak-Vance, Margaret A., Perry, William, Peskind, Elaine, Petersen, Ronald C., Pierce, Aimee, Poon, Wayne W., Potter, Huntington, Quinn, Joseph F., Raj, Ashok, Raj, Towfique, Raskind, Murray, Reiman, Eric M., Reisberg, Barry, Reitz, Christiane, Ringman, John M., Roberson, Erik D., Rosen, Howard J., Rosenberg, Roger N., Sager, Mark A., Sano, Mary, Saykin, Andrew J., Schellenberg, Gerard D., Schneider, Julie A., Schneider, Lon S., Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Swerdlow, Russell H., Tanzi, Rudolph E., Thornton-Wells, Tricia A., Trojanowski, John Q., Troncoso, Juan C., Tsuang, Debby W., Valladares, Otto, Van Deerlin, Vivianna M., Van Eldik, Linda J., Vardarajan, Badri N., Vinters, Harry V., Vonsattel, Jean Paul, Wang, Li-San, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Williamson, Jennifer, Wingo, Thomas S., Wishnek, Sarah, Woltjer, Randall L., Wright, Clinton B., Younkin, Steven G., Yu, Chang-En, Yu, Lei, Chauhan, Ganesh, Chu, Audrey Y., Fornage, Myriam, Bis, Joshua C., Havulinna, Aki S., Sargurupremraj, Muralidharan, Smith, Albert Vernon, Adams, Hieab H.H., Choi, Seung Hoan, Trompet, Stella, Garcia, Melissa E., Manichaikul, Ani, Teumer, Alexander, Gustafsson, Stefan, Bartz, Traci M., Bellenguez, Céline, Vidal, Jean Sebastien, Jian, Xueqiu, Kjartansson, Olafur, Wiggins, Kerri L., Satizabal, Claudia L., Xue, Flora, Ripatti, Samuli, Liu, Yongmei, Deelen, Joris, Hoed, Marcel den, Heckbert, Susan R., Rice, Kenneth, Smith, Nicholas L., Wong, Quenna, Aparicio, Hugo J., Buring, Julie E., Ridker, Paul M, Berr, Claudine, Dartigues, Jean-François, Hamsten, Anders, Magnusson, Patrik K., Pedersen, Nancy L., Lannfelt, Lars, Lind, Lars, Lindgren, Cecilia M., Morris, Andrew P., Hofman, Albert, Koudstaal, Peter J., Portegies, Marileen LP., Uitterlinden, André G., de Craen, Anton JM, Ford, Ian, Jukema, J. Wouter, Stott, David J, Allen, Norrina B., Sale, Michele M., Johnson, Andrew D, Bennett, David A., De Jager, Philip L., White, Charles C., Grabe, Hans Jörgen, Paulista Markus, Marcello Ricardo, Lopez, Oscar L, Rotter, Jerome I., Nalls, Michael A., Gottesman, Rebecca F., Griswold, Michael E., Knopman, David S., Windham, B. Gwen, Beiser, Alexa, Vartiainen, Erkki, French, Curtis R., Kurth, Tobias, Psaty, Bruce M., Harris, Tamara B., Rich, Stephen S, deStefano, Anita L., Schmidt, Carsten Oliver, Salomaa, Veikko, Mosley, Thomas H., Ingelsson, Erik, van Duijn, Cornelia M., Tzourio, Christophe, Launer, Lenore J, Ikram, M. Arfan, Chasman, Daniel I., Longstreth, W. T., Jr, Seshadri, Sudha, Debette, Stéphanie, Verhaaren, Benjamin F.J., Debette, Stéphanie, Bis, Joshua C., Smith, Jennifer A., Ikram, M. Kamran, Adams, Hieab H., Beecham, Ashley H., Rajan, Kumar B., Lopez, Lorna M., Barral, Sandra, van Buchem, Mark A., van der Grond, Jeroen, Smith, Albert V., Hegenscheid, Katrin, Aggarwal, Neelum T., de Andrade, Mariza, Atkinson, Elizabeth J., Beekman, Marian, Beiser, Alexa S., Blanton, Susan H., Boerwinkle, Eric, Brickman, Adam M., Bryan, R. Nick, Chauhan, Ganesh, Chen, Christopher P.L.H., Chouraki, Vincent, de Craen, Anton J.M., Crivello, Fabrice, Deary, Ian J., Deelen, Joris, De Jager, Philip L., Dufouil, Carole, Elkind, Mitchell S.V., Evans, Denis A., Freudenberger, Paul, Gottesman, Rebecca F., Guðnason, Vilmundur, Habes, Mohamad, Heckbert, Susan R., Heiss, Gerardo, Hilal, Saima, Hofer, Edith, Hofman, Albert, Ibrahim-Verbaas, Carla A., Knopman, David S., Lewis, Cora E., Liao, Jiemin, Liewald, David C.M., Luciano, Michelle, van der Lugt, Aad, Martinez, Oliver O., Mayeux, Richard, Mazoyer, Bernard, Nalls, Mike, Nauck, Matthias, Niessen, Wiro J., Oostra, Ben A., Psaty, Bruce M., Rice, Kenneth M., Rotter, Jerome I., von Sarnowski, Bettina, Schmidt, Helena, Schreiner, Pamela J., Schuur, Maaike, Sidney, Stephen S., Sigurdsson, Sigurdur, Slagboom, P. Eline, Stott, David J.M., van Swieten, John C., Teumer, Alexander, Töglhofer, Anna Maria, Traylor, Matthew, Trompet, Stella, Turner, Stephen T., Tzourio, Christophe, Uh, Hae-Won, Uitterlinden, André G., Vernooij, Meike W., Wang, Jing J., Wong, Tien Y., Wardlaw, Joanna M., Windham, B. Gwen, Wittfeld, Katharina, Wolf, Christiane, Wright, Clinton B., Yang, Qiong, Zhao, Wei, Zijdenbos, Alex, Jukema, J. Wouter, Sacco, Ralph L., Kardia, Sharon L.R., Amouyel, Philippe, Mosley, Thomas H., Longstreth, W. T., Jr, DeCarli, Charles C., van Duijn, Cornelia M., Schmidt, Reinhold, Launer, Lenore J., Grabe, Hans J., Seshadri, Sudha S., Ikram, M. Arfan, Fornage, Myriam, Bis, Joshua C., Kavousi, Maryam, Franceschini, Nora, Isaacs, Aaron, Abecasis, Gonçalo R, Schminke, Ulf, Post, Wendy, Smith, Albert V., Cupples, L. Adrienne, Markus, Hugh S, Schmidt, Reinhold, Huffman, Jennifer E., Lehtimäki, Terho, Baumert, Jens, Münzel, Thomas, Heckbert, Susan R., Dehghan, Abbas, North, Kari, Oostra, Ben, Bevan, Steve, Stoegerer, Eva-Maria, Hayward, Caroline, Raitakari, Olli, Meisinger, Christa, Schillert, Arne, Sanna, Serena, Völzke, Henry, Cheng, Yu-Ching, Thorsson, Bolli, Fox, Caroline S., Rice, Kenneth, Rivadeneira, Fernando, Nambi, Vijay, Halperin, Eran, Petrovic, Katja E., Peltonen, Leena, Wichmann, H. Erich, Schnabel, Renate B., Dörr, Marcus, Parsa, Afshin, Aspelund, Thor, Demissie, Serkalem, Kathiresan, Sekar, Reilly, Muredach P., Taylor, Kent, Uitterlinden, Andre, Couper, David J., Sitzer, Matthias, Kähönen, Mika, Illig, Thomas, Wild, Philipp S., Orru, Marco, Lüdemann, Jan, Shuldiner, Alan R., Eiriksdottir, Gudny, White, Charles C., Rotter, Jerome I., Hofman, Albert, Seissler, Jochen, Zeller, Tanja, Usala, Gianluca, Ernst, Florian, Launer, Lenore J., DʼAgostino, Ralph B., Sr, OʼLeary, Daniel H., Ballantyne, Christie, Thiery, Joachim, Ziegler, Andreas, Lakatta, Edward G., Chilukoti, Ravi Kumar, Harris, Tamara B., Wolf, Philip A., Psaty, Bruce M., Polak, Joseph F, Li, Xia, Rathmann, Wolfgang, Uda, Manuela, Boerwinkle, Eric, Klopp, Norman, Schmidt, Helena, Wilson, James F, Viikari, Jorma, Koenig, Wolfgang, Blankenberg, Stefan, Newman, Anne B., Witteman, Jacqueline, Heiss, Gerardo, van Duijn, Cornelia, Scuteri, Angelo, Homuth, Georg, Mitchell, Braxton D., Gudnason, Vilmundur, and O’Donnell, Christopher J.

Published
2019
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27. Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: cross-sectional findings from the AGES-Reykjavik study

Author

van Sloten, Thomas T., Mitchell, Gary F., Sigurdsson, Sigurdur, van Buchem, Mark A., Jonsson, Palmi V., Garcia, Melissa E., Harris, Tamara B., Henry, Ronald M.A., Levey, Andrew S., Stehouwer, Coen D.A., Gudnason, Vilmundur, and Launer, Lenore J.

Subjects
Depression, Mental -- Physiological aspects, Cerebrovascular disease -- Physiological aspects, Health, Psychology and mental health
Abstract

Background: Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated whether arterial stiffness is associated with depressive symptoms and whether cerebral small vessel disease contributes to this association. Methods: This cross-sectional study included a subset of participants from the AGES-Reykjavik study second examination round, which was conducted from 2007 to 2011. Arterial stiffness (carotid- femoral pulse wave velocity [CFPWV]), depressive symptoms (15-item geriatric depression scale [GDS-15]) and cerebral small vessel disease (MRI) were determined. Manifestations of cerebral small vessel disease included higher white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces and lower total brain parenchyma volume. Results: We included 2058 participants (mean age 79.6 yr; 59.0% women) in our analyses. Higher CFPWV was associated with a higher GDS-15 score, after adjustment for potential confounders (P 0.096, 95% confidence interval [CI] 0.005-0.187). Additional adjustment for white matter hyperintensity volume or subcortical infarcts attenuated the association between CFPWV and the GDS-15 score, which became nonsignificant (p > 0.05). Formal mediation tests showed that the attenuating effects of white matter hyperintensity volume and subcortical infarcts were statistically significant. Virchow-Robin spaces, cerebral microbleeds and cerebral atrophy did not explain the association between CFPWV and depressive symptoms. Limitations: Our study was limited by its cross-sectional design, which precludes any conclusions about causal mediation. Depressive symptoms were assessed by a self-report questionnaire. Conclusion: Greater arterial stiffness is associated with more depressive symptoms; this association is partly accounted for by white matter hyperintensity volume and subcortical infarcts. This study supports the hypothesis that arterial stiffness leads to depression in part via cerebral small vessel disease., Introduction Depression and depressive symptoms are frequently encountered in older individuals. (1) Depressive symptoms in older populations, even in the absence of a clinical diagnosis of depression, are associated with [...]

Published
2016
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28. GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment

Author

The LifeLines Cohort Study, Rietveld, Cornelius A., Medland, Sarah E., Derringer, Jaime, Yang, Jian, Esko, Tõnu, Martin, Nicolas W., Westra, Harm-Jan, Shakhbazov, Konstantin, Abdellaoui, Abdel, Agrawal, Arpana, Albrecht, Eva, Alizadeh, Behrooz Z., Amin, Najaf, Barnard, John, Baumeister, Sebastian E., Benke, Kelly S., Bielak, Lawrence F., Boatman, Jeffrey A., Boyle, Patricia A., Davies, Gail, de Leeuw, Christiaan, Eklund, Niina, Evans, Daniel S., Ferhmann, Rudolf, Fischer, Krista, Gieger, Christian, Gjessing, Håkon K., Hägg, Sara, Harris, Jennifer R., Hayward, Caroline, Holzapfel, Christina, Ibrahim-Verbaas, Carla A., Ingelsson, Erik, Jacobsson, Bo, Joshi, Peter K., Jugessur, Astanand, Kaakinen, Marika, Kanoni, Stavroula, Karjalainen, Juha, Kolcic, Ivana, Kristiansson, Kati, Kutalik, Zoltán, Lahti, Jari, Lee, Sang H., Lin, Peng, Lind, Penelope A., Liu, Yongmei, Lohman, Kurt, Loitfelder, Marisa, McMahon, George, Vidal, Pedro Marques, Meirelles, Osorio, Milani, Lili, Myhre, Ronny, Nuotio, Marja-Liisa, Oldmeadow, Christopher J., Petrovic, Katja E., Peyrot, Wouter J., Polašek, Ozren, Quaye, Lydia, Reinmaa, Eva, Rice, John P., Rizzi, Thais S., Schmidt, Helena, Schmidt, Reinhold, Smith, Albert V., Smith, Jennifer A., Tanaka, Toshiko, Terracciano, Antonio, van der Loos, Matthijs J. H. M., Vitart, Veronique, Völzke, Henry, Wellmann, Jürgen, Yu, Lei, Zhao, Wei, Allik, Jüri, Attia, John R., Bandinelli, Stefania, Bastardot, François, Beauchamp, Jonathan, Bennett, David A., Berger, Klaus, Bierut, Laura J., Boomsma, Dorret I., Bültmann, Ute, Campbell, Harry, Chabris, Christopher F., Cherkas, Lynn, Chung, Mina K., Cueca, Francesco, de Andrade, Mariza, De Jager, Philip L., De Neve, Jan-Emmanuel, Deary, Ian J., Dedoussis, George V., Deloukas, Panos, Dimitriou, Maria, Eiríksdóttir, Guðný, Elderson, Martin F., Eriksson, Johan G., Evans, David M., Faul, Jessica D., Ferrucci, Luigi, Garcia, Melissa E., Grönberg, Henrik, Guðnason, Vilmundur, Hall, Per, Harris, Juliette M., Harris, Tamara B., Hastie, Nicholas D., Heath, Andrew C., Hernandez, Dena G., Hoffmann, Wolfgang, Hofman, Adriaan, Holle, Rolf, Holliday, Elizabeth G., Hottenga, Jouke-Jan, Iacono, William G., Illig, Thomas, Järvelin, Marjo-Riitta, Kähönen, Mika, Kaprio, Jaakko, Kirkpatrick, Robert M., Kowgier, Matthew, Latvala, Antti, Launer, Lenore J., Lawior, Debbie A., Lehtimäki, Terho, Li, Jingmei, Lichtenstein, Paul, Lichtner, Peter, Liewald, David C., Madden, Pamela A., Magnusson, Patrik K. E., Mäkinen, Tomi E., Masala, Marco, McGue, Matt, Metspalu, Andres, Mielck, Andreas, Miller, Michael B., Montgomery, Grant W., Mukherjee, Sutapa, Nyholt, Dale R., Oostra, Ben A., Palmer, Lyle J., Palotie, Aarno, Penninx, Brenda W. J. H., Perola, Markus, Peyser, Patricia A., Preisig, Martin, Räikkönen, Katri, Raitakari, Olli T., Realo, Anu, Ring, Susan M., Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sarin, Antti-Pekka, Schlessinger, David, Scott, Rodney J., Snieder, Harold, St Pourcain, Beate, Starr, John M., Sul, Jae Hoon, Surakka, Ida, Svento, Rauli, Teumer, Alexander, Tiemeier, Henning, van Rooij, Frank J. A., Van Wagoner, David R., Vartiainen, Erkki, Viikari, Jorma, Vollenweider, Peter, Vonk, Judith M., Waeber, Gérard, Weir, David R., Wichmann, H.-Erich, Widen, Elisabeth, Willemsen, Gonneke, Wilson, James F., Wright, Alan F., Conley, Dalton, Davey-Smith, George, Franke, Lude, Groenen, Patrick J. F., Hofman, Albert, Johannesson, Magnus, Kardia, Sharon L. R., Krueger, Robert F., Laibson, David, Martin, Nicholas G., Meyer, Michelle N., Posthuma, Danielle, Thurik, A. Roy, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., Visscher, Peter M., Benjamin, Daniel J., Cesarini, David, and Koellinger, Philipp D.

Published
2013
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35. PLD3 variants in population studies

Author

van der Lee, Sven J., Holstege, Henne, Wong, Tsz Hang, Jakobsdottir, Johanna, Bis, Joshua C., Chouraki, Vincent, van Rooij, Jeroen G. J., Grove, Megan L., Smith, Albert V., Amin, Najaf, Choi, Seung-Hoan, Beiser, Alexa S., Garcia, Melissa E., van IJcken, Wilfred F. J., Pijnenburg, Yolande A. L., Louwersheimer, Eva, Brouwer, Rutger W. W., van den Hout, Mirjam C. G. N., Oole, Edwin, Eirkisdottir, Gudny, Levy, Daniel, Rotter, Jerome I., Emilsson, Valur, OʼDonnell, Christopher J., Aspelund, Thor, Uitterlinden, Andre G., Launer, Lenore J., Hofman, Albert, Boerwinkle, Eric, Psaty, Bruce M., DeStefano, Anita L., Scheltens, Philip, Seshadri, Sudha, van Swieten, John C., Gudnason, Vilmundur, van der Flier, Wiesje M., Ikram, Arfan M., and van Duijn, Cornelia M.

Published
2015
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36. Genetic studies of body mass index yield new insights for obesity biology

Author

Locke, Adam E., Kahali, Bratati, Berndt, Sonja I., Justice, Anne E., Pers, Tune H., Day, Felix R., Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L., Yang, Jian, Croteau-Chonka, Damien C., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltán, Luan, Jianʼan, Mägi, Reedik, Randall, Joshua C., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Faul, Jessica D., Smith, Jennifer A., Hua Zhao, Jing, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Åsa K., Karjalainen, Juha, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L., Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B., Feenstra, Bjarke, Feitosa, Mary F., Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U., Kanoni, Stavroula, Kleber, Marcus E., Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Medland, Sarah E., Nalls, Michael A., Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Shungin, Dmitry, Stančáková, Alena, Strawbridge, Rona J., Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V., Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Attwood, Antony P., Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N., Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blagieva, Roza, Blüher, Matthias, Böhringer, Stefan, Bonnycastle, Lori L., Böttcher, Yvonne, Boyd, Heather A., Bruinenberg, Marcel, Caspersen, Ida H., Ida Chen, Yii-Der, Clarke, Robert, Warwick Daw, E., de Craen, Anton J. M., Delgado, Graciela, Dimitriou, Maria, Doney, Alex S. F., Eklund, Niina, Estrada, Karol, Eury, Elodie, Folkersen, Lasse, Fraser, Ross M., Garcia, Melissa E., Geller, Frank, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Goodall, Alison H., Gordon, Scott D., Gorski, Mathias, Grabe, Hans-Jörgen, Grallert, Harald, Grammer, Tanja B., Gräler, Jürgen, Grönberg, Henrik, Groves, Christopher J., Gusto, Gaëlle, Haessler, Jeffrey, Hall, Per, Haller, Toomas, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heard-Costa, Nancy L., Helmer, Quinta, Hengstenberg, Christian, Holmen, Oddgeir, Hottenga, Jouke-Jan, James, Alan L., Jeff, Janina M., Johansson, Åsa, Jolley, Jennifer, Juliusdottir, Thorhildur, Kinnunen, Leena, Koenig, Wolfgang, Koskenvuo, Markku, Kratzer, Wolfgang, Laitinen, Jaana, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindström, Jaana, Sin Lo, Ken, Lobbens, Stéphane, Lorbeer, Roberto, Lu, Yingchang, Mach, François, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., McLachlan, Stela, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Moayyeri, Alireza, Monda, Keri L., Morken, Mario A., Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Musk, Arthur W., Nagaraja, Ramaiah, Nöthen, Markus M., Nolte, Ilja M., Pilz, Stefan, Rayner, Nigel W., Renstrom, Frida, Rettig, Rainer, Ried, Janina S., Ripke, Stephan, Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R., Scott, William R., Seufferlein, Thomas, Shi, Jianxin, Vernon Smith, Albert, Smolonska, Joanna, Stanton, Alice V., Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tyrer, Jonathan P., Uh, Hae-Won, Vandenput, Liesbeth, Verhulst, Frank C., Vermeulen, Sita H., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Warren, Helen R., Waterworth, Dawn, Weedon, Michael N., Wilkens, Lynne R., Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Wright, Alan F., Zhang, Qunyuan, Brennan, Eoin P., Choi, Murim, Dastani, Zari, Drong, Alexander W., Eriksson, Per, Franco-Cereceda, Anders, Gådin, Jesper R., Gharavi, Ali G., Goddard, Michael E., Handsaker, Robert E., Huang, Jinyan, Karpe, Fredrik, Kathiresan, Sekar, Keildson, Sarah, Kiryluk, Krzysztof, Kubo, Michiaki, Lee, Jong-Young, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McCarroll, Steven A., McKnight, Amy J., Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Okada, Yukinori, Perry, John R. B., Dorajoo, Rajkumar, Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Scott, Robert A., Stolk, Lisette, Takahashi, Atsushi, Tanaka, Toshihiro, vanʼt Hooft, Ferdinand M., Vinkhuyzen, Anna A. E., Westra, Harm-Jan, Zheng, Wei, Zondervan, Krina T., Heath, Andrew C., Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Bovet, Pascal, Campbell, Harry, Caulfield, Mark J., Cesana, Giancarlo, Chakravarti, Aravinda, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Crawford, Dana C., Adrienne Cupples, L., Cusi, Daniele, Danesh, John, de Faire, Ulf, den Ruijter, Hester M., Dominiczak, Anna F., Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G., Farrall, Martin, Felix, Stephan B., Ferrannini, Ele, Ferrières, Jean, Ford, Ian, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gejman, Pablo V., Gieger, Christian, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Alistair S., Harris, Tamara B., Hattersley, Andrew T., Hicks, Andrew A., Hindorff, Lucia A., Hingorani, Aroon D., Hofman, Albert, Homuth, Georg, Kees Hovingh, G., Humphries, Steve E., Hunt, Steven C., Hyppönen, Elina, Illig, Thomas, Jacobs, Kevin B., Jarvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Johansen, Berit, Jousilahti, Pekka, Wouter Jukema, J., Jula, Antti M., Kaprio, Jaakko, Kastelein, John J. P., Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Knekt, Paul, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Moll, Frans L., Morris, Andrew D., Morris, Andrew P., Murray, Jeffrey C., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Madden, Pamela A. F., Pasterkamp, Gerard, Peden, John F., Peters, Annette, Postma, Dirkje S., Pramstaller, Peter P., Price, Jackie F., Qi, Lu, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Rioux, John D., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schunkert, Heribert, Schwarz, Peter E. H., Sever, Peter, Shuldiner, Alan R., Sinisalo, Juha, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Trégouët, David-Alexandre, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Willemsen, Gonneke, Witteman, Jacqueline C., Carola Zillikens, M., Adair, Linda S., Amouyel, Philippe, Asselbergs, Folkert W., Assimes, Themistocles L., Bochud, Murielle, Boehm, Bernhard O., Boerwinkle, Eric, Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Cauchi, Stéphane, Chambers, John C., Chanock, Stephen J., Cooper, Richard S., de Bakker, Paul I. W., Dedoussis, George, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Groop, Leif C., Haiman, Christopher A., Hamsten, Anders, Hui, Jennie, Hunter, David J., Hveem, Kristian, Kaplan, Robert C., Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Martin, Nicholas G., März, Winfried, Melbye, Mads, Metspalu, Andres, Moebus, Susanne, Munroe, Patricia B., Njølstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sattar, Naveed, Schadt, Eric E., Schlessinger, David, Eline Slagboom, P., Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wichmann, H-Erich, Wilson, James F., Zanen, Pieter, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Heid, Iris M., OʼConnell, Jeffrey R., Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Abecasis, Gonçalo R., Franke, Lude, Frayling, Timothy M., McCarthy, Mark I., Visscher, Peter M., Scherag, André, Willer, Cristen J., Boehnke, Michael, Mohlke, Karen L., Lindgren, Cecilia M., Beckmann, Jacques S., Barroso, Inês, North, Kari E., Ingelsson, Erik, Hirschhorn, Joel N., Loos, Ruth J. F., and Speliotes, Elizabeth K.

Published
2015
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38. A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the cohorts for heart and aging research in genomic epidemiology consortium

Author

Newman, Anne B., Walter, Stefan, Lunetta, Kathryn L., Garcia, Melissa E., Slagboom, Eline, Christensen, Kaare, Arnold, Alice M., Aspelund, Thor, Aulchenko, Yurii S., Benjamin, Emelia J., Christiansen, Lene, D'Agostino, Ralph B., Sr., Fitzpatrick, Annette L., Franceschini, Nora, Glazer, Nicole L., Gudnason, Vilmundur, Hofman, Albert, Kaplan, Robert, Karasik, David, Kelly-Hayes, Margaret, Kiel, Douglas E., Launer, Lenore J., Marciante, Kristin D., Massaro, Joseph M., Miljkovic, Iva, Nalls, Michael A., Hernandez, Dena, Psaty, Bruce M., Rivadeneira, Fernando, Rotter, Jerome, Seshadri, Sudha, Smith, Albert V., Taylor, Kent D., Tiemeier, Henning, Uh, Hae-Won, Uitterlinden, Andre G., Vaupel, James W., Walston, Jeremy, Westendorp, Rudi G.J., Harris, Tamara B., Lumley, Thomas, van Duijn, Cornelia M., and Murabito, Joanne M.

Subjects
Genomics -- Research, Single nucleotide polymorphisms -- Research, Longevity -- Health aspects, Longevity -- Genetic aspects, Health, Seniors
Abstract

Background. Genome-wide association studies (GWAS) may yield insights into longevity. Methods. We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/ Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. Results. There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x [10.sup.-8]. Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x [10.sup.-7] for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. Conclusion. Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings. Key Words: Longevity--Genome-wide association study--Meta-analysis. doi: 10.1093/gerona/glq028

Published
2010

40. rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis

Author

Teo, Kevin, primary, Abeysekera, Kushala W.M., additional, Adams, Leon, additional, Aigner, Elmar, additional, Anstee, Quentin M., additional, Banales, Jesus M., additional, Banerjee, Rajarshi, additional, Basu, Priyadarshi, additional, Berg, Thomas, additional, Bhatnagar, Pallav, additional, Buch, Stephan, additional, Canbay, Ali, additional, Caprio, Sonia, additional, Chatterjee, Ankita, additional, Ida Chen, Yii-Der, additional, Chowdhury, Abhijit, additional, Daly, Ann K., additional, Datz, Christian, additional, de Gracia Hahn, Dana, additional, DiStefano, Johanna K., additional, Dong, Jiawen, additional, Duret, Amedine, additional, Emdin, Connor, additional, Fairey, Madison, additional, Gerhard, Glenn S., additional, Guo, Xiuqing, additional, Hampe, Jochen, additional, Hickman, Matthew, additional, Heintz, Lena, additional, Hudert, Christian, additional, Hunter, Harriet, additional, Kelly, Matt, additional, Kozlitina, Julia, additional, Krawczyk, Marcin, additional, Lammert, Frank, additional, Langenberg, Claudia, additional, Lavine, Joel, additional, Li, Lin, additional, Lim, Hong Kai, additional, Loomba, Rohit, additional, Luukkonen, Panu K., additional, Melton, Phillip E., additional, Mori, Trevor A., additional, Palmer, Nicholette D., additional, Parisinos, Constantinos A., additional, Pillai, Sreekumar G., additional, Qayyum, Faiza, additional, Reichert, Matthias C., additional, Romeo, Stefano, additional, Rotter, Jerome I., additional, Im, Yu Ri, additional, Santoro, Nicola, additional, Schafmayer, Clemens, additional, Speliotes, Elizabeth K., additional, Stender, Stefan, additional, Stickel, Felix, additional, Still, Christopher D., additional, Strnad, Pavel, additional, Taylor, Kent D., additional, Tybjærg-Hansen, Anne, additional, Umano, Giuseppina Rosaria, additional, Utukuri, Mrudula, additional, Valenti, Luca, additional, Wagenknecht, Lynne E., additional, Wareham, Nicholas J., additional, Watanabe, Richard M., additional, Wattacheril, Julia, additional, Yaghootkar, Hanieh, additional, Yki-Järvinen, Hannele, additional, Young, Kendra A., additional, Mann, Jake P., additional, Vreugdenhil, Anita, additional, Alisi, Anna, additional, Socha, Piotr, additional, Jańczyk, Wojciech, additional, Baumann, Ulrich, additional, Rajwal, Sanjay, additional, van Mourik, Indra, additional, Lacaille, Florence, additional, Dabbas, Myriam, additional, Kelly, Deirdre A., additional, Nobili, Valerio, additional, Eiriksdottir, Gudny, additional, Garcia, Melissa E., additional, Gudnason, Vilmundur, additional, Harris, Tamara B., additional, Kim, Lauren J., additional, Launer, Lenore J., additional, Nalls, Michael A., additional, Smith, Albert V., additional, Clark, Jeanne M., additional, Hernaez, Ruben, additional, Kao, W.H. Linda, additional, Mitchell, Braxton D., additional, Shuldiner, Alan R., additional, Yerges-Armstrong, Laura M., additional, Borecki, Ingrid B., additional, Carr, J. Jeffrey, additional, Feitosa, Mary F., additional, Wu, Jun, additional, Butler, Johannah L., additional, Fox, Caroline S., additional, Hirschhorn, Joel N., additional, Hoffmann, Udo, additional, Hwang, Shih-Jen, additional, Massaro, Joseph M., additional, O'Donnell, Christopher J., additional, Palmer, Cameron D., additional, and Sahani, Dushyant V., additional

Published
2021
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41. Investigation of seven proposed regions of linkage in multiple sclerosis: an American and French collaborative study

Author

Pericak-Vance, Margaret A., Rimmler, Jackie B., Haines, Jonathan L., Garcia, Melissa E., Oksenberg, Jorge R., Barcellos, Lisa F., Lincoln, Robin, Hauser, Stephen L., Cournu-Rebeix, Isabelle, Azoulay-Cayla, Ariele, Lyon-Caen, Olivier, Fontaine, Bertrand, Duhamel, Emmanuelle, Coppin, Helene, Brassat, David, Roth, Marie-Paule, Clanet, Michel, Alizadeh, Mehdi, Yaouanq, Jacqueline, Quelvennec, Erwann, Semana, Gilbert, Edan, Gilles, Babron, Marie-Claude, Genin, Emmanuelle, and Clerget-Darpoux, Francoise

Published
2004
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42. GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment

Author

Rietveld, Cornelius A., Medland, Sarah E., Derringer, Jaime, Yang, Jian, Esko, Tõnu, Martin, Nicolas W., Westra, Harm-Jan, Shakhbazov, Konstantin, Abdellaoui, Abdel, Agrawal, Arpana, Albrecht, Eva, Alizadeh, Behrooz Z., Amin, Najaf, Barnard, John, Baumeister, Sebastian E., Benke, Kelly S., Bielak, Lawrence F., Boatman, Jeffrey A., Boyle, Patricia A., Davies, Gail, de Leeuw, Christiaan, Eklund, Niina, Evans, Daniel S., Ferhmann, Rudolf, Fischer, Krista, Gieger, Christian, Gjessing, Håkon K., Hägg, Sara, Harris, Jennifer R., Hayward, Caroline, Holzapfel, Christina, Ibrahim-Verbaas, Carla A., Ingelsson, Erik, Jacobsson, Bo, Joshi, Peter K., Jugessur, Astanand, Kaakinen, Marika, Kanoni, Stavroula, Karjalainen, Juha, Kolcic, Ivana, Kristiansson, Kati, Kutalik, Zoltán, Lahti, Jari, Lee, Sang H., Lin, Peng, Lind, Penelope A., Liu, Yongmei, Lohman, Kurt, Loitfelder, Marisa, McMahon, George, Vidal, Pedro Marques, Meirelles, Osorio, Milani, Lili, Myhre, Ronny, Nuotio, Marja-Liisa, Oldmeadow, Christopher J., Petrovic, Katja E., Peyrot, Wouter J., Polašek, Ozren, Quaye, Lydia, Reinmaa, Eva, Rice, John P., Rizzi, Thais S., Schmidt, Helena, Schmidt, Reinhold, Smith, Albert V., Smith, Jennifer A., Tanaka, Toshiko, Terracciano, Antonio, van der Loos, Matthijs J. H. M., Vitart, Veronique, Völzke, Henry, Wellmann, Jürgen, Yu, Lei, Zhao, Wei, Allik, Jüri, Attia, John R., Bandinelli, Stefania, Bastardot, François, Beauchamp, Jonathan, Bennett, David A., Berger, Klaus, Bierut, Laura J., Boomsma, Dorret I., Bültmann, Ute, Campbell, Harry, Chabris, Christopher F., Cherkas, Lynn, Chung, Mina K., Cucca, Francesco, de Andrade, Mariza, De Jager, Philip L, De Neve, Jan-Emmanuel, Deary, Ian J., Dedoussis, George V., Deloukas, Panos, Dimitriou, Maria, Eiríksdóttir, Guöný, Elderson, Martin F., Eriksson, Johan G., Evans, David M., Faul, Jessica D., Ferrucci, Luigi, Garcia, Melissa E., Grönberg, Henrik, Guönason, Vilmundur, Hall, Per, Harris, Juliette M., Harris, Tamara B., Hastie, Nicholas D., Heath, Andrew C., Hernandez, Dena G., Hoffmann, Wolfgang, Hofman, Adriaan, Holle, Rolf, Holliday, Elizabeth G., Hottenga, Jouke-Jan, Iacono, William G., Illig, Thomas, Järvelin, Marjo-Riitta, Kähönen, Mika, Kaprio, Jaakko, Kirkpatrick, Robert M., Kowgier, Matthew, Latvala, Antti, Launer, Lenore J., Lawlor, Debbie A., Lehtimäki, Terho, Li, Jingmei, Lichtenstein, Paul, Lichtner, Peter, Liewald, David C., Madden, Pamela A., Magnusson, Patrik K. E., Mäkinen, Tomi E., Masala, Marco, McGue, Matt, Metspalu, Andres, Mielck, Andreas, Miller, Michael B., Montgomery, Grant W., Mukherjee, Sutapa, Nyholt, Dale R., Oostra, Ben A., Palmer, Lyle J., Palotie, Aarno, Penninx, Brenda W. J. H., Perola, Markus, Peyser, Patricia A, Preisig, Martin, Räikkönen, Katri, Raitakari, Olli T., Realo, Anu, Ring, Susan M., Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sarin, Antti-Pekka, Schlessinger, David, Scott, Rodney J., Snieder, Harold, Pourcain, Beate St, Starr, John M., Sul, Jae Hoon, Surakka, Ida, Svento, Rauli, Teumer, Alexander, Tiemeier, Henning, van Rooij, Frank J. A., Van Wagoner, David R., Vartiainen, Erkki, Viikari, Jorma, Vollenweider, Peter, Vonk, Judith M., Waeber, Gérard, Weir, David R., Wichmann, H.-Erich, Widen, Elisabeth, Willemsen, Gonneke, Wilson, James F., Wright, Alan F., Conley, Dalton, Davey-Smith, George, Franke, Lude, Groenen, Patrick J. F., Hofman, Albert, Johannesson, Magnus, Kardia, Sharon L R., Krueger, Robert F., Laibson, David, Martin, Nicholas G., Meyer, Michelle N., Posthuma, Danielle, Thurik, Roy A., Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., Visscher, Peter M., Benjamin, Daniel J., Cesarini, David, and Koellinger, Philipp D.

Published
2013
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45. Linkage analysis of candidate myelin genes in familial multiple sclerosis

Author

Seboun, Eric, Oksenberg, Jorge R., Rombos, Antony, Usuku, Koishiro, Goodkin, Donald E., Lincoln, Robin R., Wong, Michael, Pham-Dinh, D., Boesplug-Tanguy, O., Carsique, R., Fitoussi, R., Gartioux, C., Reyes, C., Ribierre, F., Faure, S., Fizames, C., Gyapay, G., Weissenbach, J., Dautigny, A., Rimmler, Jackie B., Garcia, Melissa E., Pericak-Vance, Margaret A., Haines, Jonathan L., Hauser, S. L., and The Multiple Sclerosis Genetics Group

Published
1999
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46. Genetic studies of leptin concentrations implicate leptin in the regulation of early adiposity

Author

Admin, Ada, primary, Yaghootkar, Hanieh, primary, Zhang, Yiying, primary, Spracklen, Cassandra N, primary, Karaderi, Tugce, primary, Huang, Lam Opal, primary, Bradfield, Jonathan, primary, Schurmann, Claudia, primary, Fine, Rebecca S, primary, Preuss, Michael H, primary, Kutalik, Zoltan, primary, Wittemans, Laura BL, primary, Lu, Yingchang, primary, Metz, Sophia, primary, Willems, Sara M, primary, Li-Gao, Ruifang, primary, Grarup, Niels, primary, Wang, Shuai, primary, Molnos, Sophie, primary, Sandoval-Zárate, América A, primary, Nalls, Mike A, primary, Lange, Leslie A, primary, Haesser, Jeffrey, primary, Guo, Xiuqing, primary, Lyytikäinen, Leo-Pekka, primary, Feitosa, Mary F, primary, Sitlani, Colleen M, primary, Venturini, Cristina, primary, Mahajan, Anubha, primary, Kacprowski, Tim, primary, Wang, Carol A, primary, Chasman, Daniel I, primary, Amin, Najaf, primary, Broer, Linda, primary, Robertson, Neil, primary, Young, Kristin L, primary, Allison, Matthew, primary, Blüher, Matthias, primary, Borja, Judith B, primary, Bork-Jensen, Jette, primary, Carrasquilla, Germán D, primary, Christofidou, Paraskevi, primary, Demirkan, Ayse, primary, Doege, Claudia A, primary, Garcia, Melissa E, primary, Graff, Mariaelisa, primary, Guo, Kaiying, primary, Hakonarson, Hakon, primary, Hong, Jaeyoung, primary, Chen, Yii-Der Ida, primary, Jackson, Rebecca, primary, Jakupović, Hermina, primary, Jousilahti, Pekka, primary, Justice, Anne E, primary, Kähönen, Mika, primary, Kizer, Jorge R, primary, Kriebe, Jennifer, primary, LeDuc, Charles A, primary, Li, Jin, primary, Lind, Lars, primary, Luan, Jian’an, primary, Mackey, David, primary, Mangino, Massimo, primary, Männistö, Satu, primary, Carli, Jayne F Martin, primary, Medina-Gomez, Carolina, primary, Mook-Kanamori, Dennis O, primary, Morris, Andrew P, primary, Mutsert, Renée de, primary, Nauck, Matthias, primary, Nedeljkovic, Ivana, primary, Pennell, Craig E, primary, Pradhan, Arund D, primary, Psaty, Bruce M, primary, Raitakari, Olli T, primary, Scott, Robert A, primary, Skaaby, Tea, primary, Strauch, Konstantin, primary, Taylor, Kent D, primary, Teumer, Alexander, primary, Uitterlinden, Andre G, primary, Wu, Ying, primary, Yao, Jie, primary, Walker, Mark, primary, North, Kari E, primary, Kovacs, Peter, primary, Ikram, M. Arfan, primary, Duijn, Cornelia M van, primary, Ridker, Paul M, primary, Lye, Stephen, primary, Homuth, Georg, primary, Ingelsson, Erik, primary, Spector, Tim D, primary, McKnight, Barbara, primary, Province, Michael A, primary, Lehtimäki, Terho, primary, Adair, Linda S, primary, Rotter, Jerome I, primary, Reiner, Alexander P, primary, Wilson, James G, primary, Harris, Tamara B, primary, Ripatti, Samuli, primary, Grallert, Harald, primary, Meigs, James B, primary, Salomaa, Veikko, primary, Hansen, Torben, primary, Dijk, Ko Willems van, primary, Wareham, Nicholas J, primary, Grant, Struan FA, primary, Langenberg, Claudia, primary, Frayling, Timothy M, primary, Lindgren, Cecilia M, primary, Mohlke, Karen L, primary, Leibel, Rudolph L, primary, Loos, Ruth JF, primary, and Kilpeläinen, Tuomas O, primary

Published
2020
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50. Correction: 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 B. L., 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, Frayling, Timothy M., Kilpeläinen, Tuomas O., Lindgren, Cecilia M., Loos, Ruth J. F., and Mohlke, Karen L.

Subjects
SDG 3 - Good Health and Well-being
Published
2019

Catalog

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