190 results on '"Maschio, Andrea"'
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2. Region-specific changes in gene expression are associated with cognitive deficits in the alpha-synuclein-induced model of Parkinson's disease: A transcriptomic profiling study
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Manchinu, Maria Francesca, Pala, Mauro, Palmas, Maria Francesca, Diana, Maria Antonietta, Maschio, Andrea, Etzi, Michela, Pisanu, Augusta, Diana, Francesca Isabella, Marongiu, Jacopo, Mansueto, Silvia, Carboni, Ezio, Fusco, Giuliana, De Simone, Alfonso, and Carta, Anna R.
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- 2024
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3. The Women4Health (W4H) cohort: A unique cohort to study women-specific mechanisms of cardio-metabolic regulation
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Busonero, Fabio, primary, Lenarduzzi, Stefania, additional, Crobu, Francesca, additional, Gentile, Roberta Maria, additional, Carta, Andrea, additional, Cracco, Francesco, additional, Maschio, Andrea, additional, Camarda, Silvia, additional, Marongiu, Michele, additional, Zanetti, Daniela, additional, Conversano, Claudio, additional, Di Lorenzo, Giovanni, additional, Mazzà, Daniela, additional, De Seta, Francesco, additional, Girotto, Giorgia, additional, and Sanna, Serena, additional
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- 2024
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- View/download PDF
4. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium
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van den Berg, Stéphanie M, de Moor, Marleen HM, Verweij, Karin JH, Krueger, Robert F, Luciano, Michelle, Arias Vasquez, Alejandro, Matteson, Lindsay K, Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D, Hansell, Narelle K, Hart, Amy B, Seppälä, Ilkka, Huffman, Jennifer E, Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abdellaoui, Abdel, Abecasis, Goncalo R, Adkins, Daniel E, Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B, Busonero, Fabio, Campbell, Harry, Costa, Paul T, Smith, George Davey, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E, Eriksson, Johan G, Fedko, Iryna O, Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M, Heath, Andrew C, Heinonen, Kati, Henders, Anjali K, Homuth, Georg, Hottenga, Jouke-Jan, Iacono, William G, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P, Kirkpatrick, Matthew G, Latvala, Antti, Lehtimäki, Terho, Liewald, David C, Madden, Pamela AF, Magri, Chiara, Magnusson, Patrik KE, Marten, Jonathan, Maschio, Andrea, Mbarek, Hamdi, Medland, Sarah E, Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W, Nauck, Matthias, Nivard, Michel G, Ouwens, Klaasjan G, Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T, Realo, Anu, Rose, Richard J, Ruggiero, Daniela, Schmidt, Carsten O, Slutske, Wendy S, Sorice, Rossella, Starr, John M, St Pourcain, Beate, Sutin, Angelina R, Timpson, Nicholas J, Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J, Zgaga, Lina, Generation Scotland, Porteous, David, Minelli, Alessandra, and Palmer, Abraham A
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Biological Psychology ,Epidemiology ,Health Sciences ,Psychology ,Genetics ,Human Genome ,Prevention ,2.1 Biological and endogenous factors ,Generic health relevance ,Cohort Studies ,Extraversion ,Psychological ,Genome-Wide Association Study ,Humans ,Multifactorial Inheritance ,Personality ,Polymorphism ,Single Nucleotide ,Risk Factors ,Generation Scotland ,Common genetic variants ,Imputation ,Phenotype harmonization ,Polygenic risk ,Zoology ,Neurosciences ,Genetics & Heredity ,Biomedical and clinical sciences ,Health sciences - Abstract
Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
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- 2016
5. Region-specific changes in gene expression are associated with cognitive deficits in the alpha-synuclein-induced model of Parkinson's disease: A transcriptomic profiling study
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Manchinu, Maria Francesca, primary, Pala, Mauro, additional, Palmas, Maria Francesca, additional, Diana, Maria Antonietta, additional, Maschio, Andrea, additional, Etzi, Michela, additional, Pisanu, Augusta, additional, Diana, Francesca Isabella, additional, Marongiu, Jacopo, additional, Mansueto, Silvia, additional, Carboni, Ezio, additional, Fusco, Giuliana, additional, De Simone, Alfonso, additional, and Carta, Anna R., additional
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- 2023
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6. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder
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de Moor, Marleen HM, van den Berg, Stéphanie M, Verweij, Karin JH, Krueger, Robert F, Luciano, Michelle, Vasquez, Alejandro Arias, Matteson, Lindsay K, Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D, Hansell, Narelle K, Hart, Amy B, Seppälä, Ilkka, Huffman, Jennifer E, Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abecasis, Goncalo R, Adkins, Daniel E, Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B, Busonero, Fabio, Campbell, Harry, Costa, Paul T, Smith, George Davey, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E, Eriksson, Johan G, Fedko, Iryna O, Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M, Heath, Andrew C, Heinonen, Kati, Henders, Anjali K, Homuth, Georg, Hottenga, Jouke-Jan, Iacono, William G, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P, Kirkpatrick, Matthew G, Latvala, Antti, Lehtimäki, Terho, Liewald, David C, Madden, Pamela AF, Magri, Chiara, Magnusson, Patrik KE, Marten, Jonathan, Maschio, Andrea, Medland, Sarah E, Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W, Nauck, Matthias, Ouwens, Klaasjan G, Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T, Realo, Anu, Rose, Richard J, Ruggiero, Daniela, Schmidt, Carsten O, Slutske, Wendy S, Sorice, Rossella, Starr, John M, St Pourcain, Beate, Sutin, Angelina R, Timpson, Nicholas J, Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J, Zgaga, Lina, Porteous, David, Minelli, Alessandra, Palmer, Abraham A, Rujescu, Dan, Ciullo, Marina, Hayward, Caroline, and Rudan, Igor
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Biological Sciences ,Genetics ,Biological Psychology ,Epidemiology ,Social and Personality Psychology ,Health Sciences ,Psychology ,Human Genome ,Brain Disorders ,Depression ,Mental Health ,Mental Illness ,Serious Mental Illness ,Major Depressive Disorder ,2.1 Biological and endogenous factors ,Mental health ,Adaptor Proteins ,Signal Transducing ,Anxiety Disorders ,Cell Adhesion Molecules ,Cell Adhesion Molecules ,Neuronal ,Depressive Disorder ,Major ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Guanylate Kinases ,Humans ,Multifactorial Inheritance ,Neuroticism ,Personality ,Polymorphism ,Single Nucleotide ,Risk Factors ,Genetics of Personality Consortium ,Other Medical and Health Sciences ,Cognitive Sciences ,Clinical sciences ,Clinical and health psychology - Abstract
ImportanceNeuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).ObjectivesTo identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.Design, setting, and participantsGenome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.Main outcomes and measuresNeuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.ResultsA genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12
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- 2015
7. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.
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Genetics of Personality Consortium, de Moor, Marleen HM, van den Berg, Stéphanie M, Verweij, Karin JH, Krueger, Robert F, Luciano, Michelle, Arias Vasquez, Alejandro, Matteson, Lindsay K, Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D, Hansell, Narelle K, Hart, Amy B, Seppälä, Ilkka, Huffman, Jennifer E, Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abecasis, Goncalo R, Adkins, Daniel E, Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B, Busonero, Fabio, Campbell, Harry, Costa, Paul T, Davey Smith, George, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E, Eriksson, Johan G, Fedko, Iryna O, Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M, Heath, Andrew C, Heinonen, Kati, Henders, Anjali K, Homuth, Georg, Hottenga, Jouke-Jan, Iacono, William G, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P, Kirkpatrick, Matthew G, Latvala, Antti, Lehtimäki, Terho, Liewald, David C, Madden, Pamela AF, Magri, Chiara, Magnusson, Patrik KE, Marten, Jonathan, Maschio, Andrea, Medland, Sarah E, Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W, Nauck, Matthias, Ouwens, Klaasjan G, Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T, Realo, Anu, Rose, Richard J, Ruggiero, Daniela, Schmidt, Carsten O, Slutske, Wendy S, Sorice, Rossella, Starr, John M, St Pourcain, Beate, Sutin, Angelina R, Timpson, Nicholas J, Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J, Zgaga, Lina, Porteous, David, Minelli, Alessandra, Palmer, Abraham A, Rujescu, Dan, Ciullo, Marina, and Hayward, Caroline
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Genetics of Personality Consortium ,Humans ,Genetic Predisposition to Disease ,Cell Adhesion Molecules ,Neuronal ,Risk Factors ,Personality ,Anxiety Disorders ,Depressive Disorder ,Major ,Multifactorial Inheritance ,Polymorphism ,Single Nucleotide ,Genome-Wide Association Study ,Neuroticism ,Adaptor Proteins ,Signal Transducing ,Cell Adhesion Molecules ,Guanylate Kinases ,Neuronal ,Depressive Disorder ,Major ,Polymorphism ,Single Nucleotide ,Adaptor Proteins ,Signal Transducing ,Other Medical and Health Sciences ,Psychology ,Cognitive Sciences - Abstract
ImportanceNeuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).ObjectivesTo identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.Design, setting, and participantsGenome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.Main outcomes and measuresNeuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.ResultsA genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12
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- 2015
8. Population genomic analysis of ancient and modern genomes yields new insights into the genetic ancestry of the Tyrolean Iceman and the genetic structure of Europe.
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Sikora, Martin, Carpenter, Meredith L, Moreno-Estrada, Andres, Henn, Brenna M, Underhill, Peter A, Sánchez-Quinto, Federico, Zara, Ilenia, Pitzalis, Maristella, Sidore, Carlo, Busonero, Fabio, Maschio, Andrea, Angius, Andrea, Jones, Chris, Mendoza-Revilla, Javier, Nekhrizov, Georgi, Dimitrova, Diana, Theodossiev, Nikola, Harkins, Timothy T, Keller, Andreas, Maixner, Frank, Zink, Albert, Abecasis, Goncalo, Sanna, Serena, Cucca, Francesco, and Bustamante, Carlos D
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Humans ,Genetics ,Population ,Polymorphism ,Single Nucleotide ,Genome ,Human ,Fossils ,Europe ,Female ,Human Genome ,Genetics ,Developmental Biology - Abstract
Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture.
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- 2014
9. The Women4Health cohort: a unique cohort to study women-specific mechanisms of cardio-metabolic regulation.
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Busonero, Fabio, Lenarduzzi, Stefania, Crobu, Francesca, Gentile, Roberta Marie, Carta, Andrea, Cracco, Francesco, Maschio, Andrea, Camarda, Silvia, Marongiu, Michele, Zanetti, Daniela, Conversano, Claudio, Di Lorenzo, Giovanni, Mazzà, Daniela, De Seta, Francesco, Girotto, Giorgia, and Sanna, Serena
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GUT microbiome ,LIPID metabolism ,COHORT analysis ,GASTROINTESTINAL hormones ,SEX hormones - Abstract
Aims: Epidemiological research has shown relevant differences between sexes in clinical manifestations, severity, and progression of cardiovascular and metabolic disorders. To date, the mechanisms underlying these differences remain unknown. Given the rising incidence of such diseases, gender-specific research on established and emerging risk factors, such as dysfunction of glycaemic and/or lipid metabolism, of sex hormones and of gut microbiome, is of paramount importance. The relationships between sex hormones, gut microbiome, and host glycaemic and/or lipid metabolism are largely unknown even in the homoeostasis status. Yet this knowledge gap would be pivotal to pinpoint to key mechanisms that are likely to be disrupted in disease context. Methods and results: Here we present the Women4Health (W4H) cohort, a unique cohort comprising up to 300 healthy women followed up during a natural menstrual cycle, set up with the primary goal to investigate the combined role of sex hormones and gut microbiota variations in regulating host lipid and glucose metabolism during homoeostasis, using a multi-omics strategy. Additionally, the W4H cohort will take into consideration another ecosystem that is unique to women, the vaginal microbiome, investigating its interaction with gut microbiome and exploring-for the first time-its role in cardiometabolic disorders. Conclusion: The W4H cohort study lays a foundation for improving current knowledge of women-specific mechanisms in cardiometabolic regulation. It aspires to transform insights on host-microbiota interactions into prevention and therapeutic approaches for personalized health care. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Genomic history of the Sardinian population
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Chiang, Charleston W. K., Marcus, Joseph H., Sidore, Carlo, Biddanda, Arjun, Al-Asadi, Hussein, Zoledziewska, Magdalena, Pitzalis, Maristella, Busonero, Fabio, Maschio, Andrea, Pistis, Giorgio, Steri, Maristella, Angius, Andrea, Lohmueller, Kirk E., Abecasis, Goncalo R., Schlessinger, David, Cucca, Francesco, and Novembre, John
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- 2018
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11. GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology
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Agencia Estatal de Investigación (España), European Commission, Junta de Andalucía, Universidad de Sevilla, Fundación Ramón Areces, Marongiu, Michele, Pérez-Mejías, Gonzalo, Orrù, Valeria, Steri, Maristella, Sidore, Carlo, Díaz-Quintana, Antonio, Mulas, Antonella, Busonero, Fabio, Maschio, Andrea, Walter, Klaudia, Tardaguila, Manuel, Akbari, Parsa, Soranzo, Nicole, Fiorillo, Edoardo, Gorospe, Myriam, Schlessinger, David, Díaz-Moreno, Irene, Cucca, Francesco, Zoledziewska, Magdalena, Agencia Estatal de Investigación (España), European Commission, Junta de Andalucía, Universidad de Sevilla, Fundación Ramón Areces, Marongiu, Michele, Pérez-Mejías, Gonzalo, Orrù, Valeria, Steri, Maristella, Sidore, Carlo, Díaz-Quintana, Antonio, Mulas, Antonella, Busonero, Fabio, Maschio, Andrea, Walter, Klaudia, Tardaguila, Manuel, Akbari, Parsa, Soranzo, Nicole, Fiorillo, Edoardo, Gorospe, Myriam, Schlessinger, David, Díaz-Moreno, Irene, Cucca, Francesco, and Zoledziewska, Magdalena
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Few genome-wide association studies (GWAS) analyzing genetic regulation of morphological traits of white blood cells have been reported. We carried out a GWAS of 12 morphological traits in 869 individuals from the general population of Sardinia, Italy. These traits, included measures of cell volume, conductivity and light scatter in four white-cell populations (eosinophils, lymphocytes, monocytes, neutrophils). This analysis yielded seven statistically significant signals, four of which were novel (four novel, PRG2, P2RX3, two of CDK6). Five signals were replicated in the independent INTERVAL cohort of 11 822 individuals. The most interesting signal with large effect size on eosinophil scatter (P-value = 8.33 x 10-32, beta = -1.651, se = 0.1351) falls within the innate immunity cluster on chromosome 11, and is located in the PRG2 gene. Computational analyses revealed that a rare, Sardinian-specific PRG2:p.Ser148Pro mutation modifies PRG2 amino acid contacts and protein dynamics in a manner that could possibly explain the changes observed in eosinophil morphology. Our discoveries shed light on genetics of morphological traits. For the first time, we describe such large effect size on eosinophils morphology that is relatively frequent in Sardinian population.
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- 2023
12. GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology
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Marongiu, Michele, primary, Pérez-Mejías, Gonzalo, additional, Orrù, Valeria, additional, Steri, Maristella, additional, Sidore, Carlo, additional, Díaz-Quintana, Antonio, additional, Mulas, Antonella, additional, Busonero, Fabio, additional, Maschio, Andrea, additional, Walter, Klaudia, additional, Tardaguila, Manuel, additional, Akbari, Parsa, additional, Soranzo, Nicole, additional, Fiorillo, Edoardo, additional, Gorospe, Myriam, additional, Schlessinger, David, additional, Díaz-Moreno, Irene, additional, Cucca, Francesco, additional, and Zoledziewska, Magdalena, additional
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- 2022
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13. Low-Pass DNA Sequencing of 1200 Sardinians Reconstructs European Y-Chromosome Phylogeny
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Francalacci, Paolo, Morelli, Laura, Angius, Andrea, Berutti, Riccardo, Reinier, Frederic, Atzeni, Rossano, Pilu, Rosella, Busonero, Fabio, Maschio, Andrea, Zara, Ilenia, Sanna, Daria, Useli, Antonella, Urru, Maria Francesca, Marcelli, Marco, Cusano, Roberto, Oppo, Manuela, Zoledziewska, Magdalena, Pitzalis, Maristella, Deidda, Francesca, Porcu, Eleonora, Poddie, Fausto, Kang, Hyun Min, Lyons, Robert, Tarrier, Brendan, Gresham, Jennifer Bragg, Li, Bingshan, Tofanelli, Sergio, Alonso, Santos, Dei, Mariano, Lai, Sandra, Mulas, Antonella, Whalen, Michael B., Uzzau, Sergio, Jones, Chris, Schlessinger, David, Abecasis, Gonçalo R., Sanna, Serena, Sidore, Carlo, and Cucca, Francesco
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- 2013
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14. GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology.
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Marongiu, Michele, Pérez-Mejías, Gonzalo, Orrù, Valeria, Steri, Maristella, Sidore, Carlo, Díaz-Quintana, Antonio, Mulas, Antonella, Busonero, Fabio, Maschio, Andrea, Walter, Klaudia, Tardaguila, Manuel, Akbari, Parsa, Soranzo, Nicole, Fiorillo, Edoardo, Gorospe, Myriam, Schlessinger, David, Díaz-Moreno, Irene, Cucca, Francesco, and Zoledziewska, Magdalena
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- 2023
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15. Genome-Wide Association Study Shows BCL11A Associated with Persistent Fetal Hemoglobin and Amelioration of the Phenotype of β-Thalassemia
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Uda, Manuela, Galanello, Renzo, Sanna, Serena, Lettre, Guillaume, Sankaran, Vijay G., Chen, Weimin, Usala, Gianluca, Busonero, Fabio, Maschio, Andrea, Albai, Giuseppe, Piras, Maria Grazia, Sestu, Natascia, Lai, Sandra, Dei, Mariano, Mulas, Antonella, Crisponi, Laura, Naitza, Silvia, Asunis, Isadora, Deiana, Manila, Nagaraja, Ramaiah, Perseu, Lucia, Satta, Stefania, Cipollina, Maria Dolores, Sollaino, Carla, Moi, Paolo, Hirschhorn, Joel N., Orkin, Stuart H., Abecasis, Gonçalo R., Schlessinger, David, and Cao, Antonio
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- 2008
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16. Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function
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Arnaud-Lopez, Lisette, Usala, Gianluca, Ceresini, Graziano, Mitchell, Braxton D., Pilia, Maria Grazia, Piras, Maria Grazia, Sestu, Natascia, Maschio, Andrea, Busonero, Fabio, Albai, Giuseppe, Dei, Mariano, Lai, Sandra, Mulas, Antonella, Crisponi, Laura, Tanaka, Toshiko, Bandinelli, Stefania, Guralnik, Jack M., Uda, Manuela, Abecasis, Goncalo R., Nagaraja, Ramaiah, Sanna, Serena, and Naitza, Silvia
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Sardinians -- Genetic aspects ,Thyrotropin -- Research ,Thyrotropin -- Genetic aspects ,Thyroid diseases -- Genetic aspects ,Biological sciences - Abstract
A study was conducted to genotype 362, 129 SNPs in 4,300 Sardinians and identifies a strong association between alleles of rs4704397 and circulating thyroid-stimulating hormone (TSH) levels. Results revealed that PDE8B, by affecting cAMP concentrations in the thyroid, might alter thyroid-hormone levels in the serum and affect TSH release from the pituitary and thus might modulate thyroid physiology and the course of thyroid disease.
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- 2008
17. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of [beta]-thalassemia
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Uda, Manuela, Galanello, Renzo, Sanna, Serena, Lettre, Guillaume, Sankaran, Vijay G., Chen, Weimin, Usala, Gianluca, Busonero, Fabio, Maschio, Andrea, Albai, Giuseppe, Piras, Maria Grazia, Sestu, Natascia, Lai, Sandra, Dei, Mariano, Mulas, Antonella, Crisponi, Laura, Naitza, Silvia, Asunis, Isadora, Deiana, Manila, Nagaraja, Ramaiah, Perseu, Lucia, Satta, Stefania, Cipollina, Maria Dolores, Sollaino, Carla, Moi, Paolo, Hirschhorn, Joel N., Orkin, Stuart H., Abecasis, Goncalo R., Schlessinger, David, and Cao, Antonio
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Fetal hemoglobin -- Genetic aspects ,Thalassemia -- Genetic aspects ,Protein research -- Reports ,Science and technology - Abstract
[beta]-Thalassemia and sickle cell disease both display a great deal of phenotypic heterogeneity, despite being generally thought of as simple Mendelian diseases. The reasons for this are not well understood, although the level of fetal hemoglobin (HbF) is one well characterized ameliorating factor in both of these conditions. To better understand the genetic basis of this heterogeneity, we carried out genome-wide scans with 362,129 common SNPs on 4,305 Sardinians to look for genetic linkage and association with HbF levels, as well as other red blood cell-related traits. Among major variants affecting HbF levels, SNP rs11886868 in the BCL11A gene was strongly associated with this trait (P < [10-.sup.35]). The C allele frequency was significantly higher in Sardinian individuals with elevated HbF levels, detected by screening for [beta]-thalassemia, and patients with attenuated forms of [beta]-thalassemia vs. those with thalassemia major. We also show that the same BCL11A variant is strongly associated with HbF levels in a large cohort of sickle cell patients. These results indicate that BCL11A variants, by modulating HbF levels, act as an important ameliorating factor of the [beta]-thalassemia phenotype, and it is likely they could help ameliorate other hemoglobin disorders. We expect our findings will help to characterize the molecular mechanisms of fetal globin regulation and could eventually contribute to the development of new therapeutic approaches for [beta]-thalassemia and sickle cell anemia. globin gene regulation | polymorphism | sickle cell anemia
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- 2008
18. IRAK-M is involved in the pathogenesis of early onset persistent asthma
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Balaci, Lenuta, Spada, Maria Cristina, Malerba, Giovanni, Bisognin, Andrea, Trabetti, Elisabetta, Boner, Attilio, Pescollderungg, Lydia, Pignatti, Pier Franco, Schlessinger, David, Cao, Antonio, Pilia, Giuseppe, Olla, Nazario, Pelosi, Umberto, Corrias, Adriano, Perra, Roberto, Torrazza, Pier Luigi, Pirina, Pietro, Ginesu, Francesco, Marcias, Silvano, Schintu, Maria Grazia, Del Giacco, Gennaro Sergio, Manconi, Paolo Emilio, Sole, Gabriella, Sanna, Serena, Masala, Marco, Crisponi, Laura, Fattori, Matilde, Devoto, Marcella, Doratiotto, Silvia, Rassu, Stefania, Mereu, Simonetta, Giua, Enrico, Cadeddu, Natalina Graziella, Atzeni, Roberto, Loddo, Laura, Anedda, Francesca, Naitza, Silvia, Zuncheddu, Maria Antonietta, Maschio, Andrea, Altea, Daniele, Uda, Manuela, and Pilia, Sabrina
- Subjects
Asthma -- Genetic aspects ,Asthma -- Research ,Human immunogenetics -- Research ,Single nucleotide polymorphisms -- Research ,Biological sciences - Abstract
Affected Sardinian families were studied to elucidate the genetic components of asthma by linkage and association analysis at chromosome 12q13-24. It was found that variants in the interleukin-1 receptor associated kinase-M gene are associated with early-onset persistent asthma and indicate interleukin-1 receptor associated kinase-M gene as a potential target for therapeutic intervention against asthma.
- Published
- 2007
19. An integrated map of genetic variation from 1,092 human genomes
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McVean, Gil A., Altshuler, David M., Durbin, Richard M., Abecasis, Gonçalo R., Bentley, David R., Chakravarti, Aravinda, Clark, Andrew G., Donnelly, Peter, Eichler, Evan E., Flicek, Paul, Gabriel, Stacey B., Gibbs, Richard A., Green, Eric D., Hurles, Matthew E., Knoppers, Bartha M., Korbel, Jan O., Lander, Eric S., Lee, Charles, Lehrach, Hans, Mardis, Elaine R., Marth, Gabor T., Nickerson, Deborah A., Schmidt, Jeanette P., Sherry, Stephen T., Wang, Jun, Wilson, Richard K., Dinh, Huyen, Kovar, Christie, Lee, Sandra, Lewis, Lora, Muzny, Donna, Reid, Jeff, Wang, Min, Wang, Jun, Fang, Xiaodong, Guo, Xiaosen, Jian, Min, Jiang, Hui, Jin, Xin, Li, Guoqing, Li, Jingxiang, Li, Yingrui, Li, Zhuo, Liu, Xiao, Lu, Yao, Ma, Xuedi, Su, Zhe, Tai, Shuaishuai, Tang, Meifang, Wang, Bo, Wang, Guangbiao, Wu, Honglong, Wu, Renhua, Yin, Ye, Zhang, Wenwei, Zhao, Jiao, Zhao, Meiru, Zheng, Xiaole, Zhou, Yan, Lander, Eric S., Gabriel, Stacey B., Gupta, Namrata, Flicek, Paul, Clarke, Laura, Leinonen, Rasko, Smith, Richard E., Zheng-Bradley, Xiangqun, Bentley, David R., Grocock, Russell, Humphray, Sean, James, Terena, Kingsbury, Zoya, Lehrach, Hans, Sudbrak, Ralf, Albrecht, Marcus W., Amstislavskiy, Vyacheslav S., Borodina, Tatiana A., Lienhard, Matthias, Mertes, Florian, Sultan, Marc, Timmermann, Bernd, Yaspo, Marie-Laure, Sherry, Stephen T., McVean, Gil A., Mardis, Elaine R., Wilson, Richard K., Fulton, Lucinda, Fulton, Robert, Weinstock, George M., Durbin, Richard M., Balasubramaniam, Senduran, Burton, John, Danecek, Petr, Keane, Thomas M., Kolb-Kokocinski, Anja, McCarthy, Shane, Stalker, James, Quail, Michael, Schmidt, Jeanette P., Davies, Christopher J., Gollub, Jeremy, Webster, Teresa, Wong, Brant, Zhan, Yiping, Auton, Adam, Yu, Fuli, Bainbridge, Matthew, Challis, Danny, Evani, Uday S., Lu, James, Nagaswamy, Uma, Sabo, Aniko, Wang, Yi, Yu, Jin, Coin, Lachlan J. M., Fang, Lin, Li, Qibin, Li, Zhenyu, Lin, Haoxiang, Liu, Binghang, Luo, Ruibang, Qin, Nan, Shao, Haojing, Wang, Bingqiang, Xie, Yinlong, Ye, Chen, Yu, Chang, Zhang, Fan, Zheng, Hancheng, Zhu, Hongmei, Garrison, Erik P., Kural, Deniz, Lee, Wan-Ping, Fung Leong, Wen, Ward, Alistair N., Wu, Jiantao, Zhang, Mengyao, Lee, Charles, Griffin, Lauren, Hsieh, Chih-Heng, Mills, Ryan E., Shi, Xinghua, von Grotthuss, Marcin, Zhang, Chengsheng, Daly, Mark J., DePristo, Mark A., Banks, Eric, Bhatia, Gaurav, Carneiro, Mauricio O., del Angel, Guillermo, Genovese, Giulio, Handsaker, Robert E., Hartl, Chris, McCarroll, Steven A., Nemesh, James C., Poplin, Ryan E., Schaffner, Stephen F., Shakir, Khalid, Yoon, Seungtai C., Lihm, Jayon, Makarov, Vladimir, Jin, Hanjun, Kim, Wook, Cheol Kim, Ki, Korbel, Jan O., Rausch, Tobias, Beal, Kathryn, Cunningham, Fiona, Herrero, Javier, McLaren, William M., Ritchie, Graham R. S., Clark, Andrew G., Gottipati, Srikanth, Keinan, Alon, Rodriguez-Flores, Juan L., Sabeti, Pardis C., Grossman, Sharon R., Tabrizi, Shervin, Tariyal, Ridhi, Cooper, David N., Ball, Edward V., Stenson, Peter D., Barnes, Bret, Bauer, Markus, Keira Cheetham, R., Cox, Tony, Eberle, Michael, Kahn, Scott, Murray, Lisa, Peden, John, Shaw, Richard, Ye, Kai, Batzer, Mark A., Konkel, Miriam K., Walker, Jerilyn A., MacArthur, Daniel G., Lek, Monkol, Sudbrak, Herwig, Ralf, Shriver, Mark D., Bustamante, Carlos D., Byrnes, Jake K., De La Vega, Francisco M., Gravel, Simon, Kenny, Eimear E., Kidd, Jeffrey M., Lacroute, Phil, Maples, Brian K., Moreno-Estrada, Andres, Zakharia, Fouad, Halperin, Eran, Baran, Yael, Craig, David W., Christoforides, Alexis, Homer, Nils, Izatt, Tyler, Kurdoglu, Ahmet A., Sinari, Shripad A., Squire, Kevin, Xiao, Chunlin, Sebat, Jonathan, Bafna, Vineet, Ye, Kenny, Burchard, Esteban G., Hernandez, Ryan D., Gignoux, Christopher R., Haussler, David, Katzman, Sol J., James Kent, W., Howie, Bryan, Ruiz-Linares, Andres, Dermitzakis, Emmanouil T., Lappalainen, Tuuli, Devine, Scott E., Liu, Xinyue, Maroo, Ankit, Tallon, Luke J., Rosenfeld, Jeffrey A., Min Kang, Hyun, Anderson, Paul, Angius, Andrea, Bigham, Abigail, Blackwell, Tom, Busonero, Fabio, Cucca, Francesco, Fuchsberger, Christian, Jones, Chris, Jun, Goo, Li, Yun, Lyons, Robert, Maschio, Andrea, Porcu, Eleonora, Reinier, Fred, Sanna, Serena, Schlessinger, David, Sidore, Carlo, Tan, Adrian, Kate Trost, Mary, Awadalla, Philip, Hodgkinson, Alan, Lunter, Gerton, McVean, Gil A., Marchini, Jonathan L., Myers, Simon, Churchhouse, Claire, Delaneau, Olivier, Gupta-Hinch, Anjali, Iqbal, Zamin, Mathieson, Iain, Rimmer, Andy, Xifara, Dionysia K., Oleksyk, Taras K., Fu, Yunxin, Liu, Xiaoming, Xiong, Momiao, Jorde, Lynn, Witherspoon, David, Xing, Jinchuan, Eichler, Evan E., Browning, Brian L., Alkan, Can, Hajirasouliha, Iman, Hormozdiari, Fereydoun, Ko, Arthur, Sudmant, Peter H., Mardis, Elaine R., Chen, Ken, Chinwalla, Asif, Ding, Li, Dooling, David, Koboldt, Daniel C., McLellan, Michael D., Wallis, John W., Wendl, Michael C., Zhang, Qunyuan, Hurles, Matthew E., Tyler-Smith, Chris, Albers, Cornelis A., Ayub, Qasim, Chen, Yuan, Coffey, Alison J., Colonna, Vincenza, Huang, Ni, Jostins, Luke, Li, Heng, Scally, Aylwyn, Walter, Klaudia, Xue, Yali, Zhang, Yujun, Gerstein, Mark B., Abyzov, Alexej, Balasubramanian, Suganthi, Chen, Jieming, Clarke, Declan, Fu, Yao, Habegger, Lukas, Harmanci, Arif O., Jin, Mike, Khurana, Ekta, Jasmine Mu, Xinmeng, Sisu, Cristina, Lee, Charles, McCarroll, Steven A., Degenhardt, Jeremiah, Korbel, Jan O., Stütz, Adrian M., Church, Deanna, Michaelson, Jacob J., Eichler, Evan E., Hurles, Matthew E., Blackburne, Ben, Lindsay, Sarah J., Ning, Zemin, DePristo, Mark A., Min Kang, Hyun, Mardis, Elaine R., Yu, Fuli, Michelson, Leslie P., Tyler-Smith, Chris, Frankish, Adam, Harrow, Jennifer, Fowler, Gerald, Hale, Walker, Kalra, Divya, Flicek, Paul, Clarke, Laura, Barker, Jonathan, Kelman, Gavin, Kulesha, Eugene, Radhakrishnan, Rajesh, Roa, Asier, Smirnov, Dmitriy, Streeter, Ian, Toneva, Iliana, Vaughan, Brendan, Sherry, Stephen T., Ananiev, Victor, Belaia, Zinaida, Beloslyudtsev, Dimitriy, Bouk, Nathan, Chen, Chao, Cohen, Robert, Cook, Charles, Garner, John, Hefferon, Timothy, Kimelman, Mikhail, Liu, Chunlei, Lopez, John, Meric, Peter, OʼSullivan, Chris, Ostapchuk, Yuri, Phan, Lon, Ponomarov, Sergiy, Schneider, Valerie, Shekhtman, Eugene, Sirotkin, Karl, Slotta, Douglas, Zhang, Hua, Chakravarti, Aravinda, Knoppers, Bartha M., Barnes, Kathleen C., Beiswanger, Christine, Burchard, Esteban G., Bustamante, Carlos D., Cai, Hongyu, Cao, Hongzhi, Durbin, Richard M., Gharani, Neda, Henn, Brenna, Jones, Danielle, Jorde, Lynn, Kaye, Jane S., Kent, Alastair, Kerasidou, Angeliki, Mathias, Rasika, Ossorio, Pilar N., Parker, Michael, Reich, David, Rotimi, Charles N., Royal, Charmaine D., Sandoval, Karla, Su, Yeyang, Sudbrak, Ralf, Tian, Zhongming, Tishkoff, Sarah, Toji, Lorraine H., Tyler-Smith, Chris, Via, Marc, Wang, Yuhong, Yang, Huanming, Yang, Ling, Zhu, Jiayong, Bodmer, Walter, Bedoya, Gabriel, Ruiz-Linares, Andres, Zhi Ming, Cai, Yang, Gao, Jia You, Chu, Peltonen, Leena, Garcia-Montero, Andres, Orfao, Alberto, Dutil, Julie, Martinez-Cruzado, Juan C., Oleksyk, Taras K., Brooks, Lisa D., Felsenfeld, Adam L., McEwen, Jean E., Clemm, Nicholas C., Duncanson, Audrey, Dunn, Michael, Guyer, Mark S., Peterson, Jane L., Abecasis, Goncalo R., and Auton, Adam
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- 2012
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20. New gene functions in megakaryopoiesis and platelet formation
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Gieger, Christian, Radhakrishnan, Aparna, Cvejic, Ana, Tang, Weihong, Porcu, Eleonora, Pistis, Giorgio, Serbanovic-Canic, Jovana, Elling, Ulrich, Goodall, Alison H., Labrune, Yann, Lopez, Lorna M., Mägi, Reedik, Meacham, Stuart, Okada, Yukinori, Pirastu, Nicola, Sorice, Rossella, Teumer, Alexander, Voss, Katrin, Zhang, Weihua, Ramirez-Solis, Ramiro, Bis, Joshua C., Ellinghaus, David, Gögele, Martin, Hottenga, Jouke-Jan, Langenberg, Claudia, Kovacs, Peter, O’Reilly, Paul F., Shin, So-Youn, Esko, Tõnu, Hartiala, Jaana, Kanoni, Stavroula, Murgia, Federico, Parsa, Afshin, Stephens, Jonathan, van der Harst, Pim, Ellen van der Schoot, C., Allayee, Hooman, Attwood, Antony, Balkau, Beverley, Bastardot, François, Basu, Saonli, Baumeister, Sebastian E., Biino, Ginevra, Bomba, Lorenzo, Bonnefond, Amélie, Cambien, François, Chambers, John C., Cucca, Francesco, D’Adamo, Pio, Davies, Gail, de Boer, Rudolf A., de Geus, Eco J. C., Döring, Angela, Elliott, Paul, Erdmann, Jeanette, Evans, David M., Falchi, Mario, Feng, Wei, Folsom, Aaron R., Frazer, Ian H., Gibson, Quince D., Glazer, Nicole L., Hammond, Chris, Hartikainen, Anna-Liisa, Heckbert, Susan R., Hengstenberg, Christian, Hersch, Micha, Illig, Thomas, Loos, Ruth J. F., Jolley, Jennifer, Tee Khaw, Kay, Kühnel, Brigitte, Kyrtsonis, Marie-Christine, Lagou, Vasiliki, Lloyd-Jones, Heather, Lumley, Thomas, Mangino, Massimo, Maschio, Andrea, Mateo Leach, Irene, McKnight, Barbara, Memari, Yasin, Mitchell, Braxton D., Montgomery, Grant W., Nakamura, Yusuke, Nauck, Matthias, Navis, Gerjan, Nöthlings, Ute, Nolte, Ilja M., Porteous, David J., Pouta, Anneli, Pramstaller, Peter P., Pullat, Janne, Ring, Susan M., Rotter, Jerome I., Ruggiero, Daniela, Ruokonen, Aimo, Sala, Cinzia, Samani, Nilesh J., Sambrook, Jennifer, Schlessinger, David, Schreiber, Stefan, Schunkert, Heribert, Scott, James, Smith, Nicholas L., Snieder, Harold, Starr, John M., Stumvoll, Michael, Takahashi, Atsushi, Tang, Wilson W.H., Taylor, Kent, Tenesa, Albert, Lay Thein, Swee, Tönjes, Anke, Uda, Manuela, Ulivi, Sheila, van Veldhuisen, Dirk J., Visscher, Peter M., Völker, Uwe, Wichmann, Erich H., Wiggins, Kerri L., Willemsen, Gonneke, Yang, Tsun-Po, Hua Zhao, Jing, Zitting, Paavo, Bradley, John R., Dedoussis, George V., Gasparini, Paolo, Hazen, Stanley L., Metspalu, Andres, Pirastu, Mario, Shuldiner, Alan R., Joost van Pelt, L., Zwaginga, Jaap-Jan, Boomsma, Dorret I., Deary, Ian J., Franke, Andre, Froguel, Philippe, Ganesh, Santhi K., Jarvelin, Marjo-Riitta, Martin, Nicholas G., Meisinger, Christa, Psaty, Bruce M., Spector, Timothy D., Wareham, Nicholas J., Akkerman, Jan-Willem N., Ciullo, Marina, Deloukas, Panos, Greinacher, Andreas, Jupe, Steve, Kamatani, Naoyuki, Khadake, Jyoti, Kooner, Jaspal S., Penninger, Josef, Prokopenko, Inga, Stemple, Derek, Toniolo, Daniela, Wernisch, Lorenz, Sanna, Serena, Hicks, Andrew A., Rendon, Augusto, Ferreira, Manuel A., Ouwehand, Willem H., and Soranzo, Nicole
- Published
- 2011
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21. Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels
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Pichler, Irene, Minelli, Cosetta, Sanna, Serena, Tanaka, Toshiko, Schwienbacher, Christine, Naitza, Silvia, Porcu, Eleonora, Pattaro, Cristian, Busonero, Fabio, Zanon, Alessandra, Maschio, Andrea, Melville, Scott A., Grazia Piras, Maria, Longo, Dan L., Guralnik, Jack, Hernandez, Dena, Bandinelli, Stefania, Aigner, Elmar, Murphy, Anthony T., Wroblewski, Victor, Marroni, Fabio, Theurl, Igor, Gnewuch, Carsten, Schadt, Eric, Mitterer, Manfred, Schlessinger, David, Ferrucci, Luigi, Witcher, Derrick R., Hicks, Andrew A., Weiss, Günter, Uda, Manuela, and Pramstaller, Peter P.
- Published
- 2011
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22. A Sardinian founder mutation in glycoprotein Ib platelet subunit beta ( GP1BB ) that impacts thrombocytopenia
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Busonero, Fabio, primary, Steri, Maristella, additional, Orrù, Valeria, additional, Sole, Gabriella, additional, Olla, Stefania, additional, Marongiu, Michele, additional, Maschio, Andrea, additional, Sidore, Carlo, additional, Lai, Sandra, additional, Mulas, Antonella, additional, Zoledziewska, Magdalena, additional, Floris, Matteo, additional, Pala, Mauro, additional, Forabosco, Paola, additional, Asunis, Isadora, additional, Pitzalis, Maristella, additional, Deidda, Francesca, additional, Masala, Marco, additional, Caria, Cristian Antonio, additional, Barella, Susanna, additional, Abecasis, Goncalo R., additional, Schlessinger, David, additional, Sanna, Serena, additional, Fiorillo, Edoardo, additional, and Cucca, Francesco, additional
- Published
- 2020
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23. PRF1 mutation alters immune system activation, inflammation, and risk of autoimmunity
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Sidore, Carlo, primary, Orrù, Valeria, additional, Cocco, Eleonora, additional, Steri, Maristella, additional, Inshaw, Jamie RJ, additional, Pitzalis, Maristella, additional, Mulas, Antonella, additional, McGurnaghan, Stuart, additional, Frau, Jessica, additional, Porcu, Eleonora, additional, Busonero, Fabio, additional, Dei, Mariano, additional, Lai, Sandra, additional, Sole, Gabriella, additional, Virdis, Francesca, additional, Serra, Valentina, additional, Poddie, Fausto, additional, Delitala, Alessandro, additional, Marongiu, Michele, additional, Deidda, Francesca, additional, Pala, Mauro, additional, Floris, Matteo, additional, Masala, Marco, additional, Onengut-Gumuscu, Suna, additional, Robertson, Catherine C, additional, Leoni, Lidia, additional, Frongia, Annapaola, additional, Ricciardi, Maria Rossella, additional, Chessa, Margherita, additional, Olla, Nazario, additional, Lovicu, Mario, additional, Loizedda, Annalisa, additional, Maschio, Andrea, additional, Mereu, Luisa, additional, Ferrigno, Paola, additional, Curreli, Nicolo, additional, Balaci, Lenuta, additional, Loi, Francesco, additional, Ferreli, Liana AP, additional, Pilia, Maria Grazia, additional, Pani, Antonello, additional, Marrosu, Maria Giovanna, additional, Abecasis, Goncalo R, additional, Rich, Stephen S, additional, Colhoun, Helen, additional, Todd, John A, additional, Schlessinger, David, additional, Fiorillo, Edoardo, additional, Cucca, Francesco, additional, and Zoledziewska, Magdalena, additional
- Published
- 2020
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24. A Sardinian founder mutation in GP1BB that impacts thrombocytopenia
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Busonero, Fabio, primary, Steri, Maristella, additional, Orrù, Valeria, additional, Sole, Gabriella, additional, Olla, Stefania, additional, Marongiu, Michele, additional, Sidore, Carlo, additional, Lai, Sandra, additional, Mulas, Antonella, additional, Maschio, Andrea, additional, Zoledziewska, Magdalena, additional, Floris, Matteo, additional, Pala, Mauro, additional, Forabosco, Paola, additional, Asunis, Isadora, additional, Pitzalis, Maristella, additional, Deidda, Francesca, additional, Masala, Marco, additional, Caria, Cristian Antonio, additional, Barella, Susanna, additional, Abecasis, Goncalo R., additional, Schlessinger, David, additional, Sanna, Serena, additional, Fiorillo, Edoardo, additional, and Cucca, Francesco, additional
- Published
- 2020
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25. Hundreds of variants clustered in genomic loci and biological pathways affect human height
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Lango Allen, Hana, Estrada, Karol, Lettre, Guillaume, Berndt, Sonja I., Weedon, Michael N., Rivadeneira, Fernando, Willer, Cristen J., Jackson, Anne U., Vedantam, Sailaja, Raychaudhuri, Soumya, Ferreira, Teresa, Wood, Andrew R., Weyant, Robert J., Segrè, Ayellet V., Speliotes, Elizabeth K., Wheeler, Eleanor, Soranzo, Nicole, Park, Ju-Hyun, Yang, Jian, Gudbjartsson, Daniel, Heard-Costa, Nancy L., Randall, Joshua C., Qi, Lu, Vernon Smith, Albert, Mägi, Reedik, Pastinen, Tomi, Liang, Liming, Heid, Iris M., Luan, Jian’an, Thorleifsson, Gudmar, Winkler, Thomas W., Goddard, Michael E., Sin Lo, Ken, Palmer, Cameron, Workalemahu, Tsegaselassie, Aulchenko, Yurii S., Johansson, Åsa, Carola Zillikens, M., Feitosa, Mary F., Esko, Tõnu, Johnson, Toby, Ketkar, Shamika, Kraft, Peter, Mangino, Massimo, Prokopenko, Inga, Absher, Devin, Albrecht, Eva, Ernst, Florian, Glazer, Nicole L., Hayward, Caroline, Hottenga, Jouke-Jan, Jacobs, Kevin B., Knowles, Joshua W., Kutalik, Zoltán, Monda, Keri L., Polasek, Ozren, Preuss, Michael, Rayner, Nigel W., Robertson, Neil R., Steinthorsdottir, Valgerdur, Tyrer, Jonathan P., Voight, Benjamin F., Wiklund, Fredrik, Xu, Jianfeng, Hua Zhao, Jing, Nyholt, Dale R., Pellikka, Niina, Perola, Markus, Perry, John R. B., Surakka, Ida, Tammesoo, Mari-Liis, Altmaier, Elizabeth L., Amin, Najaf, Aspelund, Thor, Bhangale, Tushar, Boucher, Gabrielle, Chasman, Daniel I., Chen, Constance, Coin, Lachlan, Cooper, Matthew N., Dixon, Anna L., Gibson, Quince, Grundberg, Elin, Hao, Ke, Juhani Junttila, M., Kaplan, Lee M., Kettunen, Johannes, König, Inke R., Kwan, Tony, Lawrence, Robert W., Levinson, Douglas F., Lorentzon, Mattias, McKnight, Barbara, Morris, Andrew P., Müller, Martina, Suh Ngwa, Julius, Purcell, Shaun, Rafelt, Suzanne, Salem, Rany M., Salvi, Erika, Sanna, Serena, Shi, Jianxin, Sovio, Ulla, Thompson, John R., Turchin, Michael C., Vandenput, Liesbeth, Verlaan, Dominique J., Vitart, Veronique, White, Charles C., Ziegler, Andreas, Almgren, Peter, Balmforth, Anthony J., Campbell, Harry, Citterio, Lorena, De Grandi, Alessandro, Dominiczak, Anna, Duan, Jubao, Elliott, Paul, Elosua, Roberto, Eriksson, Johan G., Freimer, Nelson B., Geus, Eco J. C., Glorioso, Nicola, Haiqing, Shen, Hartikainen, Anna-Liisa, Havulinna, Aki S., Hicks, Andrew A., Hui, Jennie, Igl, Wilmar, Illig, Thomas, Jula, Antti, Kajantie, Eero, Kilpeläinen, Tuomas O., Koiranen, Markku, Kolcic, Ivana, Koskinen, Seppo, Kovacs, Peter, Laitinen, Jaana, Liu, Jianjun, Lokki, Marja-Liisa, Marusic, Ana, Maschio, Andrea, Meitinger, Thomas, Mulas, Antonella, Paré, Guillaume, Parker, Alex N., Peden, John F., Petersmann, Astrid, Pichler, Irene, Pietiläinen, Kirsi H., Pouta, Anneli, Ridderstråle, Martin, Rotter, Jerome I., Sambrook, Jennifer G., Sanders, Alan R., Oliver Schmidt, Carsten, Sinisalo, Juha, Smit, Jan H., Stringham, Heather M., Bragi Walters, G., Widen, Elisabeth, Wild, Sarah H., Willemsen, Gonneke, Zagato, Laura, Zgaga, Lina, Zitting, Paavo, Alavere, Helene, Farrall, Martin, McArdle, Wendy L., Nelis, Mari, Peters, Marjolein J., Ripatti, Samuli, van Meurs, Joyce B. J., Aben, Katja K., Ardlie, Kristin G., Beckmann, Jacques S., Beilby, John P., Bergman, Richard N., Bergmann, Sven, Collins, Francis S., Cusi, Daniele, den Heijer, Martin, Eiriksdottir, Gudny, Gejman, Pablo V., Hall, Alistair S., Hamsten, Anders, Huikuri, Heikki V., Iribarren, Carlos, Kähönen, Mika, Kaprio, Jaakko, Kathiresan, Sekar, Kiemeney, Lambertus, Kocher, Thomas, Launer, Lenore J., Lehtimäki, Terho, Melander, Olle, Mosley, Tom H., Jr, Musk, Arthur W., Nieminen, Markku S., O’Donnell, Christopher J., Ohlsson, Claes, Oostra, Ben, Palmer, Lyle J., Raitakari, Olli, Ridker, Paul M., Rioux, John D., Rissanen, Aila, Rivolta, Carlo, Schunkert, Heribert, Shuldiner, Alan R., Siscovick, David S., Stumvoll, Michael, Tönjes, Anke, Tuomilehto, Jaakko, van Ommen, Gert-Jan, Viikari, Jorma, Heath, Andrew C., Martin, Nicholas G., Montgomery, Grant W., Province, Michael A., Kayser, Manfred, Arnold, Alice M., Atwood, Larry D., Boerwinkle, Eric, Chanock, Stephen J., Deloukas, Panos, Gieger, Christian, Grönberg, Henrik, Hall, Per, Hattersley, Andrew T., Hengstenberg, Christian, Hoffman, Wolfgang, Mark Lathrop, G., Salomaa, Veikko, Schreiber, Stefan, Uda, Manuela, Waterworth, Dawn, Wright, Alan F., Assimes, Themistocles L., Barroso, Inês, Hofman, Albert, Mohlke, Karen L., Boomsma, Dorret I., Caulfield, Mark J., Adrienne Cupples, L., Erdmann, Jeanette, Fox, Caroline S., Gudnason, Vilmundur, Gyllensten, Ulf, Harris, Tamara B., Hayes, Richard B., Jarvelin, Marjo-Riitta, Mooser, Vincent, Munroe, Patricia B., Ouwehand, Willem H., Penninx, Brenda W., Pramstaller, Peter P., Quertermous, Thomas, Rudan, Igor, Samani, Nilesh J., Spector, Timothy D., Völzke, Henry, Watkins, Hugh, Wilson, James F., Groop, Leif C., Haritunians, Talin, Hu, Frank B., Kaplan, Robert C., Metspalu, Andres, North, Kari E., Schlessinger, David, Wareham, Nicholas J., Hunter, David J., O’Connell, Jeffrey R., Strachan, David P., Wichmann, H.-Erich, Borecki, Ingrid B., van Duijn, Cornelia M., Schadt, Eric E., Thorsteinsdottir, Unnur, Peltonen, Leena, Uitterlinden, André G., Visscher, Peter M., Chatterjee, Nilanjan, Loos, Ruth J. F., Boehnke, Michael, McCarthy, Mark I., Ingelsson, Erik, Lindgren, Cecilia M., Abecasis, Gonçalo R., Stefansson, Kari, Frayling, Timothy M., and Hirschhorn, Joel N.
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- 2010
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26. Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia
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Sanna, Serena, Busonero, Fabio, Maschio, Andrea, McArdle, Patrick F., Usala, Gianluca, Dei, Mariano, Lai, Sandra, Mulas, Antonella, Piras, Maria Grazia, Perseu, Lucia, Masala, Marco, Marongiu, Mara, Crisponi, Laura, Naitza, Silvia, Galanello, Renzo, Abecasis, Gonçalo R., Shuldiner, Alan R., Schlessinger, David, Cao, Antonio, and Uda, Manuela
- Published
- 2009
27. Relative impact of indels versus SNPs on complex disease
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Gagliano, Sarah A., primary, Sengupta, Sebanti, additional, Sidore, Carlo, additional, Maschio, Andrea, additional, Cucca, Francesco, additional, Schlessinger, David, additional, and Abecasis, Gonçalo R., additional
- Published
- 2018
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28. Exome-wide association study of plasma lipids in > 300,000 individuals
- Author
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Liu, Dajiang J., Peloso, Gina M., Yu, Haojie, Butterworth, Adam S., Wang, Xiao, Mahajan, Anubha, Saleheen, Danish, Emdin, Connor, Alam, Dewan, Alves, Alexessander Couto, Amouyel, Philippe, Di Angelantonio, Emanuele, Arveiler, Dominique, Assimes, Themistocles L., Auer, Paul L., Baber, Usman, Ballantyne, Christie M., Bang, Lia E., Benn, Marianne, Bis, Joshua C., Boehnke, Michael, Boerwinkle, Eric, Bork-Jensen, Jette, Bottinger, Erwin P., Brandslund, Ivan, Brown, Morris, Busonero, Fabio, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Y. Eugene, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Connell, John M., Cucca, Francesco, Cupples, L. Adrienne, Damrauer, Scott M., Davies, Gail, Deary, Ian J., Dedoussis, George, Denny, Joshua C., Dominiczak, Anna, Dube, Marie-Pierre, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Farmaki, Aliki-Eleni, Feitosa, Mary F., Ferrario, Marco, Ferrieres, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W., Frayling, Timothy M., Frikke-Schmidt, Ruth, Fritsche, Lars G., Frossard, Philippe, Fuster, Valentin, Ganesh, Santhi K., Gao, Wei, Garcia, Melissa E., Gieger, Christian, Giulianini, Franco, Goodarzi, Mark O., Grallert, Harald, Grarup, Niels, Groop, Leif, Grove, Megan L., Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hirschhorn, Joel N., Holmen, Oddgeir L., Huffman, Jennifer, Huo, Yong, Hveem, Kristian, Jabeen, Sehrish, Jackson, Anne U., Jakobsdottir, Johanna, Jarvelin, Marjo-Riitta, Jensen, Gorm B., Jorgensen, Marit E., Jukema, J. Wouter, Justesen, Johanne M., Kamstrup, Pia R., Kanoni, Stavroula, Karpe, Fredrik, Kee, Frank, Khera, Amit V., Klarin, Derek, Koistinen, Heikki A., Kooner, Jaspal S., Kooperberg, Charles, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo, Langenberg, Claudia, Langsted, Anne, Launer, Lenore J., Lauritzen, Torsten, Liewald, David C. M., Lin, Li An, Linneberg, Allan, Loos, Ruth J. F., Lu, Yingchang, Lu, Xiangfeng, Magi, Reedik, Malarstig, Anders, Manichaikul, Ani, Manning, Alisa K., Mantyselka, Pekka, Marouli, Eirini, Masca, Nicholas G. D., Maschio, Andrea, Meigs, James B., Melander, Olle, Metspalu, Andres, Morris, Andrew P., Morrison, Alanna C., Mulas, Antonella, Mueller-Nurasyid, Martina, Munroe, Patricia B., Neville, Matt J., Nielsen, Jonas B., Nielsen, Sune F., Nordestgaard, Borge G., Ordovas, Jose M., Mehran, Roxana, O'Donnell, Christoper J., Orho-Melander, Marju, Molony, Cliona M., Muntendam, Pieter, Padmanabhan, Sandosh, Palmer, Colin N. A., Pasko, Dorota, Patel, Aniruddh P., Pedersen, Oluf, Perola, Markus, Peters, Annette, Pisinger, Charlotta, Pistis, Giorgio, Polasek, Ozren, Poulter, Neil, Psaty, Bruce M., Rader, Daniel J., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renström, Frida, Rich, Stephen S., Ridker, Paul M., Rioux, John D., Robertson, Neil R., Roden, Dan M., Rotter, Jerome I., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Sanna, Serena, Sattar, Naveed, Schmidt, Ellen M., Scott, Robert A., Sever, Peter, Sevilla, Raquel S., Shaffer, Christian M., Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert V., Smith, Blair H., Somayajula, Sangeetha, Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stirrups, Kathleen E., Stitziel, Nathan, Strauch, Konstantin, Stringham, Heather M., Surendran, Praveen, Tada, Hayato, Tall, Alan R., Tang, Hua, Tardif, Jean-Claude, Taylor, Kent D., Trompet, Stella, Tsao, Philip S., Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, van Zuydam, Natalie R., Varbo, Anette, Varga, Tibor V., Virtamo, Jarmo, Waldenberger, Melanie, Wang, Nan, Wareham, Nick J., Warren, Helen R., Weeke, Peter E., Weinstock, Joshua, Wessel, Jennifer, Wilson, James G., Wilson, Peter W. F., Xu, Ming, Yaghootkar, Hanieh, Young, Robin, Zeggini, Eleftheria, Zhang, He, Zheng, Neil S., Zhang, Weihua, Zhang, Yan, Zhou, Wei, Zhou, Yanhua, Zoledziewska, Magdalena, Howson, Joanna M. M., Danesh, John, McCarthy, Mark I., Cowan, Chad A., Abecasis, Goncalo, Deloukas, Panos, Musunuru, Kiran, Willer, Cristen J., Kathiresan, Sekar, Liu, Dajiang J., Peloso, Gina M., Yu, Haojie, Butterworth, Adam S., Wang, Xiao, Mahajan, Anubha, Saleheen, Danish, Emdin, Connor, Alam, Dewan, Alves, Alexessander Couto, Amouyel, Philippe, Di Angelantonio, Emanuele, Arveiler, Dominique, Assimes, Themistocles L., Auer, Paul L., Baber, Usman, Ballantyne, Christie M., Bang, Lia E., Benn, Marianne, Bis, Joshua C., Boehnke, Michael, Boerwinkle, Eric, Bork-Jensen, Jette, Bottinger, Erwin P., Brandslund, Ivan, Brown, Morris, Busonero, Fabio, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Y. Eugene, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Connell, John M., Cucca, Francesco, Cupples, L. Adrienne, Damrauer, Scott M., Davies, Gail, Deary, Ian J., Dedoussis, George, Denny, Joshua C., Dominiczak, Anna, Dube, Marie-Pierre, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Farmaki, Aliki-Eleni, Feitosa, Mary F., Ferrario, Marco, Ferrieres, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W., Frayling, Timothy M., Frikke-Schmidt, Ruth, Fritsche, Lars G., Frossard, Philippe, Fuster, Valentin, Ganesh, Santhi K., Gao, Wei, Garcia, Melissa E., Gieger, Christian, Giulianini, Franco, Goodarzi, Mark O., Grallert, Harald, Grarup, Niels, Groop, Leif, Grove, Megan L., Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hirschhorn, Joel N., Holmen, Oddgeir L., Huffman, Jennifer, Huo, Yong, Hveem, Kristian, Jabeen, Sehrish, Jackson, Anne U., Jakobsdottir, Johanna, Jarvelin, Marjo-Riitta, Jensen, Gorm B., Jorgensen, Marit E., Jukema, J. Wouter, Justesen, Johanne M., Kamstrup, Pia R., Kanoni, Stavroula, Karpe, Fredrik, Kee, Frank, Khera, Amit V., Klarin, Derek, Koistinen, Heikki A., Kooner, Jaspal S., Kooperberg, Charles, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo, Langenberg, Claudia, Langsted, Anne, Launer, Lenore J., Lauritzen, Torsten, Liewald, David C. M., Lin, Li An, Linneberg, Allan, Loos, Ruth J. F., Lu, Yingchang, Lu, Xiangfeng, Magi, Reedik, Malarstig, Anders, Manichaikul, Ani, Manning, Alisa K., Mantyselka, Pekka, Marouli, Eirini, Masca, Nicholas G. D., Maschio, Andrea, Meigs, James B., Melander, Olle, Metspalu, Andres, Morris, Andrew P., Morrison, Alanna C., Mulas, Antonella, Mueller-Nurasyid, Martina, Munroe, Patricia B., Neville, Matt J., Nielsen, Jonas B., Nielsen, Sune F., Nordestgaard, Borge G., Ordovas, Jose M., Mehran, Roxana, O'Donnell, Christoper J., Orho-Melander, Marju, Molony, Cliona M., Muntendam, Pieter, Padmanabhan, Sandosh, Palmer, Colin N. A., Pasko, Dorota, Patel, Aniruddh P., Pedersen, Oluf, Perola, Markus, Peters, Annette, Pisinger, Charlotta, Pistis, Giorgio, Polasek, Ozren, Poulter, Neil, Psaty, Bruce M., Rader, Daniel J., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renström, Frida, Rich, Stephen S., Ridker, Paul M., Rioux, John D., Robertson, Neil R., Roden, Dan M., Rotter, Jerome I., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Sanna, Serena, Sattar, Naveed, Schmidt, Ellen M., Scott, Robert A., Sever, Peter, Sevilla, Raquel S., Shaffer, Christian M., Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert V., Smith, Blair H., Somayajula, Sangeetha, Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stirrups, Kathleen E., Stitziel, Nathan, Strauch, Konstantin, Stringham, Heather M., Surendran, Praveen, Tada, Hayato, Tall, Alan R., Tang, Hua, Tardif, Jean-Claude, Taylor, Kent D., Trompet, Stella, Tsao, Philip S., Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, van Zuydam, Natalie R., Varbo, Anette, Varga, Tibor V., Virtamo, Jarmo, Waldenberger, Melanie, Wang, Nan, Wareham, Nick J., Warren, Helen R., Weeke, Peter E., Weinstock, Joshua, Wessel, Jennifer, Wilson, James G., Wilson, Peter W. F., Xu, Ming, Yaghootkar, Hanieh, Young, Robin, Zeggini, Eleftheria, Zhang, He, Zheng, Neil S., Zhang, Weihua, Zhang, Yan, Zhou, Wei, Zhou, Yanhua, Zoledziewska, Magdalena, Howson, Joanna M. M., Danesh, John, McCarthy, Mark I., Cowan, Chad A., Abecasis, Goncalo, Deloukas, Panos, Musunuru, Kiran, Willer, Cristen J., and Kathiresan, Sekar
- Abstract
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
- Published
- 2017
- Full Text
- View/download PDF
29. Exome-wide association study of plasma lipids in >300,000 individuals
- Author
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Liu, Dajiang J., Peloso, Gina M., Yu, Haojie, Butterworth, Adam S., Wang, Xiao, Mahajan, Anubha, Saleheen, Danish, Emdin, Connor, Alam, Dewan, Alves, Alexessander Couto, Amouyel, Philippe, Angelantonio, Emanuele DI, Arveiler, Dominique, Assimes, Themistocles L., Auer, Paul L., Baber, Usman, Ballantyne, Christie M., Bang, Lia E., Benn, Marianne, Bis, Joshua C., Boehnke, Michael, Boerwinkle, Eric, Bork-Jensen, Jette, Bottinger, Erwin P., Brandslund, Ivan, Brown, Morris, Busonero, Fabio, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Y. Eugene, Chen, Yii Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Connell, John M., Cucca, Francesco, Cupples, L. Adrienne, Damrauer, Scott M., Davies, Gail, Deary, Ian J., Dedoussis, George, Denny, Joshua C., Dominiczak, Anna, Dubé, Marie Pierre, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Toñu, Farmaki, Aliki Eleni, Feitosa, Mary F., Ferrario, Marco, Ferrieres, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W., Frayling, Timothy M., Frikke-Schmidt, Ruth, Fritsche, Lars G., Frossard, Philippe, Fuster, Valentin, Ganesh, Santhi K., Gao, Wei, Garcia, Melissa E., Gieger, Christian, Giulianini, Franco, Goodarzi, Mark O., Grallert, Harald, Grarup, Niels, Groop, Leif, Grove, Megan L., Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hirschhorn, Joel N., Holmen, Oddgeir L., Huffman, Jennifer, Huo, Yong, Hveem, Kristian, Jabeen, Sehrish, Jackson, Anne U., Jakobsdottir, Johanna, Jarvelin, Marjo Riitta, Jensen, Gorm B., Jørgensen, Marit E., Jukema, J. Wouter, Justesen, Johanne M., Kamstrup, Pia R., Kanoni, Stavroula, Karpe, Fredrik, Kee, Frank, Khera, Amit V., Klarin, Derek, Koistinen, Heikki A., Kooner, Jaspal S., Kooperberg, Charles, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo, Langenberg, Claudia, Langsted, Anne, Launer, Lenore J., Lauritzen, Torsten, MLiewald, David C., Lin, Li An, Linneberg, Allan, Loos, Ruth J.F., Lu, Yingchang, Lu, Xiangfeng, Mägi, Reedik, Malarstig, Anders, Manichaikul, Ani, Manning, Alisa K., Mäntyselkä, Pekka, Marouli, Eirini, Masca, Nicholas G.D., Maschio, Andrea, Meigs, James B., Melander, Olle, Metspalu, Andres, Morris, Andrew P., Morrison, Alanna C., Mulas, Antonella, Müller-Nurasyid, Martina, Munroe, Patricia B., Neville, Matt J., Nielsen, Sune F., Nielsen, Jonas B., Nordestgaard, Børge G., Ordovas, Jose M., Mehran, Roxana, O'Donnell, Christoper J., Orho-Melander, Marju, Molony, Cliona M., Muntendam, Pieter, Padmanabhan, Sandosh, Palmer, Colin N.A., Pasko, Dorota, Patel, Aniruddh P., Pedersen, Oluf, Perola, Markus, Peters, Annette, Pisinger, Charlotta, Pistis, Giorgio, Polasek, Ozren, Poulter, Neil, Psaty, Bruce M., Rader, Daniel J., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renström, Frida, Rich, Stephen S., Ridker, Paul M., Rioux, John D., Robertson, Neil R., Roden, Dan M., Rotter, Jerome I., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Sanna, Serena, Sattar, Naveed, Schmidt, Ellen M., Scott, Robert A., Sever, Peter, Sevilla, Raquel S., Shaffer, Christian M., Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert V., Smith, Blair H., Somayajula, Sangeetha, Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stirrups, Kathleen E., Stitziel, Nathan, Strauch, Konstantin, Stringham, Heather M., Surendran, Praveen, Tada, Hayato, Tall, Alan R., Tang, Hua, Tardif, Jean Claude, Taylor, Kent D., Trompet, Stella, Tsao, Philip S., Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Zuydam, Natalie R.Van, Varbo, Anette, Varga, Tibor V., Virtamo, Jarmo, Waldenberger, Melanie, Wang, Nan, Wareham, Nick J., Warren, Helen R., Weeke, Peter E., Weinstock, Joshua, Wessel, Jennifer, Wilson, James G., Wilson, Peter W.F., Xu, Ming, Yaghootkar, Hanieh, Young, Robin, Zeggini, Eleftheria, Zhang, He, Zheng, Neil S., Zhang, Weihua, Zhang, Yan, Zhou, Wei, Zhou, Yanhua, Zoledziewska, Magdalena, Howson, Joanna M.M., Danesh, John, McCarthy, Mark I., Cowan, Chad A., Abecasis, Goncalo, Deloukas, Panos, Musunuru, Kiran, Willer, Cristen J., Kathiresan, Sekar, V Varga, Tibor, Liu, Dajiang J., Peloso, Gina M., Yu, Haojie, Butterworth, Adam S., Wang, Xiao, Mahajan, Anubha, Saleheen, Danish, Emdin, Connor, Alam, Dewan, Alves, Alexessander Couto, Amouyel, Philippe, Angelantonio, Emanuele DI, Arveiler, Dominique, Assimes, Themistocles L., Auer, Paul L., Baber, Usman, Ballantyne, Christie M., Bang, Lia E., Benn, Marianne, Bis, Joshua C., Boehnke, Michael, Boerwinkle, Eric, Bork-Jensen, Jette, Bottinger, Erwin P., Brandslund, Ivan, Brown, Morris, Busonero, Fabio, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Y. Eugene, Chen, Yii Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Connell, John M., Cucca, Francesco, Cupples, L. Adrienne, Damrauer, Scott M., Davies, Gail, Deary, Ian J., Dedoussis, George, Denny, Joshua C., Dominiczak, Anna, Dubé, Marie Pierre, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Toñu, Farmaki, Aliki Eleni, Feitosa, Mary F., Ferrario, Marco, Ferrieres, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W., Frayling, Timothy M., Frikke-Schmidt, Ruth, Fritsche, Lars G., Frossard, Philippe, Fuster, Valentin, Ganesh, Santhi K., Gao, Wei, Garcia, Melissa E., Gieger, Christian, Giulianini, Franco, Goodarzi, Mark O., Grallert, Harald, Grarup, Niels, Groop, Leif, Grove, Megan L., Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hirschhorn, Joel N., Holmen, Oddgeir L., Huffman, Jennifer, Huo, Yong, Hveem, Kristian, Jabeen, Sehrish, Jackson, Anne U., Jakobsdottir, Johanna, Jarvelin, Marjo Riitta, Jensen, Gorm B., Jørgensen, Marit E., Jukema, J. Wouter, Justesen, Johanne M., Kamstrup, Pia R., Kanoni, Stavroula, Karpe, Fredrik, Kee, Frank, Khera, Amit V., Klarin, Derek, Koistinen, Heikki A., Kooner, Jaspal S., Kooperberg, Charles, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo, Langenberg, Claudia, Langsted, Anne, Launer, Lenore J., Lauritzen, Torsten, MLiewald, David C., Lin, Li An, Linneberg, Allan, Loos, Ruth J.F., Lu, Yingchang, Lu, Xiangfeng, Mägi, Reedik, Malarstig, Anders, Manichaikul, Ani, Manning, Alisa K., Mäntyselkä, Pekka, Marouli, Eirini, Masca, Nicholas G.D., Maschio, Andrea, Meigs, James B., Melander, Olle, Metspalu, Andres, Morris, Andrew P., Morrison, Alanna C., Mulas, Antonella, Müller-Nurasyid, Martina, Munroe, Patricia B., Neville, Matt J., Nielsen, Sune F., Nielsen, Jonas B., Nordestgaard, Børge G., Ordovas, Jose M., Mehran, Roxana, O'Donnell, Christoper J., Orho-Melander, Marju, Molony, Cliona M., Muntendam, Pieter, Padmanabhan, Sandosh, Palmer, Colin N.A., Pasko, Dorota, Patel, Aniruddh P., Pedersen, Oluf, Perola, Markus, Peters, Annette, Pisinger, Charlotta, Pistis, Giorgio, Polasek, Ozren, Poulter, Neil, Psaty, Bruce M., Rader, Daniel J., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renström, Frida, Rich, Stephen S., Ridker, Paul M., Rioux, John D., Robertson, Neil R., Roden, Dan M., Rotter, Jerome I., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Sanna, Serena, Sattar, Naveed, Schmidt, Ellen M., Scott, Robert A., Sever, Peter, Sevilla, Raquel S., Shaffer, Christian M., Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert V., Smith, Blair H., Somayajula, Sangeetha, Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stirrups, Kathleen E., Stitziel, Nathan, Strauch, Konstantin, Stringham, Heather M., Surendran, Praveen, Tada, Hayato, Tall, Alan R., Tang, Hua, Tardif, Jean Claude, Taylor, Kent D., Trompet, Stella, Tsao, Philip S., Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Zuydam, Natalie R.Van, Varbo, Anette, Varga, Tibor V., Virtamo, Jarmo, Waldenberger, Melanie, Wang, Nan, Wareham, Nick J., Warren, Helen R., Weeke, Peter E., Weinstock, Joshua, Wessel, Jennifer, Wilson, James G., Wilson, Peter W.F., Xu, Ming, Yaghootkar, Hanieh, Young, Robin, Zeggini, Eleftheria, Zhang, He, Zheng, Neil S., Zhang, Weihua, Zhang, Yan, Zhou, Wei, Zhou, Yanhua, Zoledziewska, Magdalena, Howson, Joanna M.M., Danesh, John, McCarthy, Mark I., Cowan, Chad A., Abecasis, Goncalo, Deloukas, Panos, Musunuru, Kiran, Willer, Cristen J., Kathiresan, Sekar, and V Varga, Tibor
- Abstract
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TGrich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
- Published
- 2017
30. Overexpression of the Cytokine BAFF and Autoimmunity Risk
- Author
-
Steri, Maristella, primary, Orrù, Valeria, additional, Idda, M. Laura, additional, Pitzalis, Maristella, additional, Pala, Mauro, additional, Zara, Ilenia, additional, Sidore, Carlo, additional, Faà, Valeria, additional, Floris, Matteo, additional, Deiana, Manila, additional, Asunis, Isadora, additional, Porcu, Eleonora, additional, Mulas, Antonella, additional, Piras, Maria G., additional, Lobina, Monia, additional, Lai, Sandra, additional, Marongiu, Mara, additional, Serra, Valentina, additional, Marongiu, Michele, additional, Sole, Gabriella, additional, Busonero, Fabio, additional, Maschio, Andrea, additional, Cusano, Roberto, additional, Cuccuru, Gianmauro, additional, Deidda, Francesca, additional, Poddie, Fausto, additional, Farina, Gabriele, additional, Dei, Mariano, additional, Virdis, Francesca, additional, Olla, Stefania, additional, Satta, Maria A., additional, Pani, Mario, additional, Delitala, Alessandro, additional, Cocco, Eleonora, additional, Frau, Jessica, additional, Coghe, Giancarlo, additional, Lorefice, Lorena, additional, Fenu, Giuseppe, additional, Ferrigno, Paola, additional, Ban, Maria, additional, Barizzone, Nadia, additional, Leone, Maurizio, additional, Guerini, Franca R., additional, Piga, Matteo, additional, Firinu, Davide, additional, Kockum, Ingrid, additional, Lima Bomfim, Izaura, additional, Olsson, Tomas, additional, Alfredsson, Lars, additional, Suarez, Ana, additional, Carreira, Patricia E., additional, Castillo-Palma, Maria J., additional, Marcus, Joseph H., additional, Congia, Mauro, additional, Angius, Andrea, additional, Melis, Maurizio, additional, Gonzalez, Antonio, additional, Alarcón Riquelme, Marta E., additional, da Silva, Berta M., additional, Marchini, Maurizio, additional, Danieli, Maria G., additional, Del Giacco, Stefano, additional, Mathieu, Alessandro, additional, Pani, Antonello, additional, Montgomery, Stephen B., additional, Rosati, Giulio, additional, Hillert, Jan, additional, Sawcer, Stephen, additional, D’Alfonso, Sandra, additional, Todd, John A., additional, Novembre, John, additional, Abecasis, Gonçalo R., additional, Whalen, Michael B., additional, Marrosu, Maria G., additional, Meloni, Alessandra, additional, Sanna, Serena, additional, Gorospe, Myriam, additional, Schlessinger, David, additional, Fiorillo, Edoardo, additional, Zoledziewska, Magdalena, additional, and Cucca, Francesco, additional
- Published
- 2017
- Full Text
- View/download PDF
31. Population- and individual-specific regulatory variation in Sardinia
- Author
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Pala, Mauro, primary, Zappala, Zachary, additional, Marongiu, Mara, additional, Li, Xin, additional, Davis, Joe R, additional, Cusano, Roberto, additional, Crobu, Francesca, additional, Kukurba, Kimberly R, additional, Gloudemans, Michael J, additional, Reinier, Frederic, additional, Berutti, Riccardo, additional, Piras, Maria G, additional, Mulas, Antonella, additional, Zoledziewska, Magdalena, additional, Marongiu, Michele, additional, Sorokin, Elena P, additional, Hess, Gaelen T, additional, Smith, Kevin S, additional, Busonero, Fabio, additional, Maschio, Andrea, additional, Steri, Maristella, additional, Sidore, Carlo, additional, Sanna, Serena, additional, Fiorillo, Edoardo, additional, Bassik, Michael C, additional, Sawcer, Stephen J, additional, Battle, Alexis, additional, Novembre, John, additional, Jones, Chris, additional, Angius, Andrea, additional, Abecasis, Gonçalo R, additional, Schlessinger, David, additional, Cucca, Francesco, additional, and Montgomery, Stephen B, additional
- Published
- 2017
- Full Text
- View/download PDF
32. Mitogenome Diversity in Sardinians: A Genetic Window onto an Island's Past
- Author
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Olivieri, Anna, primary, Sidore, Carlo, additional, Achilli, Alessandro, additional, Angius, Andrea, additional, Posth, Cosimo, additional, Furtwängler, Anja, additional, Brandini, Stefania, additional, Capodiferro, Marco Rosario, additional, Gandini, Francesca, additional, Zoledziewska, Magdalena, additional, Pitzalis, Maristella, additional, Maschio, Andrea, additional, Busonero, Fabio, additional, Lai, Luca, additional, Skeates, Robin, additional, Gradoli, Maria Giuseppina, additional, Beckett, Jessica, additional, Marongiu, Michele, additional, Mazzarello, Vittorio, additional, Marongiu, Patrizia, additional, Rubino, Salvatore, additional, Rito, Teresa, additional, Macaulay, Vincent, additional, Semino, Ornella, additional, Pala, Maria, additional, Abecasis, Gonçalo R., additional, Schlessinger, David, additional, Conde-Sousa, Eduardo, additional, Soares, Pedro, additional, Richards, Martin B., additional, Cucca, Francesco, additional, and Torroni, Antonio, additional
- Published
- 2017
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33. Population history of the Sardinian people inferred from whole-genome sequencing
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Chiang, Charleston W K, primary, Marcus, Joseph H, additional, Sidore, Carlo, additional, Al-Asadi, Hussein, additional, Zoledziewska, Magdalena, additional, Pitzalis, Maristella, additional, Busonero, Fabio, additional, Maschio, Andrea, additional, Pistis, Giorgio, additional, Steri, Maristella, additional, Angius, Andrea, additional, Lohmueller, Kirk E, additional, Abecasis, Goncalo R, additional, Schlessinger, David, additional, Cucca, Francesco, additional, and Novembre, John, additional
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- 2016
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34. Genome-wide association study identifies novel locus for neuroticism and shows polygenic association with Major Depressive Disorder
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de Moor, Marleen H.M., van den Berg, Stéphanie M., Verweij, Karin J.H., Krueger, Robert F., Luciano, Michelle, Vasquez, Alejandro Arias, Matteson, Lindsay K., Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D., Hansell, Narelle K., Hart, Amy B., Seppälä, Ilkka, Huffman, Jennifer E., Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abecasis, Goncalo R., Adkins, Daniel E., Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B., Busonero, Fabio, Campbell, Harry, Costa, Paul T., Smith, George Davey, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E., Eriksson, Johan G., Fedko, Iryna O., Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M., Heath, Andrew C., Heinonen, Kati, Henders, Anjali K., Homuth, Georg, Hottenga, Jouke-Jan, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P., Kirkpatrick, Matthew G., Latvala, Antti, Lehtimäki, Terho, Liewald, David C., Madden, Pamela A.F., Magri, Chiara, Magnusson, Patrik K.E., Marten, Jonathan, Maschio, Andrea, Medland, Sarah E., Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W., Nauck, Matthias, Ouwens, Klaasjan G., Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T., Realo, Anu, Rose, Richard J., Ruggiero, Daniela, Schmidt, Carsten O., Slutske, Wendy S., Sorice, Rossella, Starr, John M., Pourcain, Beate St, Sutin, Angelina R., Timpson, Nicholas J., Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J., Zgaga, Lina, Scotland, Generation, Porteous, David, Minelli, Alessandra, Palmer, Abraham A., Rujescu, Dan, Ciullo, Marina, Hayward, Caroline, Rudan, Igor, Metspalu, Andres, Kaprio, Jaakko, Deary, Ian J., Räikkönen, Katri, Wilson, James F., Keltikangas-Järvinen, Liisa, Bierut, Laura J., Hettema, John M., Grabe, Hans J., van Duijn, Cornelia M., Evans, David M., Schlessinger, David, Pedersen, Nancy L., Terracciano, Antonio, McGue, Matt, Penninx, Brenda W.J.H., Martin, Nicholas G., and Boomsma, Dorret I.
- Subjects
Neuroticism ,Depressive Disorder, Major ,Multifactorial Inheritance ,Cell Adhesion Molecules, Neuronal ,Anxiety Disorders ,Polymorphism, Single Nucleotide ,Article ,Risk Factors ,Humans ,Genetic Predisposition to Disease ,Cell Adhesion Molecules ,Guanylate Kinases ,Adaptor Proteins, Signal Transducing ,Genome-Wide Association Study ,Personality - Abstract
Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 P .05) and MDD (4.02 × 10-9 P .05) in the 2 other cohorts.This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.
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- 2015
35. Relative impact of indels versus SNPs on complex disease.
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Gagliano, Sarah A., Sengupta, Sebanti, Sidore, Carlo, Maschio, Andrea, Cucca, Francesco, Schlessinger, David, and Abecasis, Gonçalo R.
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- 2019
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36. New gene functions in megakaryopoiesis and platelet formation
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Gieger, Christian Radhakrishnan, Aparna Cvejic, Ana Tang, Weihong Porcu, Eleonora Pistis, Giorgio Serbanovic-Canic, Jovana Elling, Ulrich Goodall, Alison H. Labrune, Yann and Lopez, Lorna M. Maegi, Reedik Meacham, Stuart Okada, Yukinori Pirastu, Nicola Sorice, Rossella Teumer, Alexander and Voss, Katrin Zhang, Weihua Ramirez-Solis, Ramiro Bis, Joshua C. Ellinghaus, David Goegele, Martin Hottenga, Jouke-Jan Langenberg, Claudia Kovacs, Peter O'Reilly, Paul F. Shin, So-Youn Esko, Toenu Hartiala, Jaana Kanoni, Stavroula Murgia, Federico Parsa, Afshin Stephens, Jonathan and van der Harst, Pim van der Schoot, C. Ellen Allayee, Hooman and Attwood, Antony Balkau, Beverley Bastardot, Francois and Basu, Saonli Baumeister, Sebastian E. Biino, Ginevra Bomba, Lorenzo Bonnefond, Amelie Cambien, Francois Chambers, John C. Cucca, Francesco D'Adamo, Pio Davies, Gail de Boer, Rudolf A. de Geus, Eco J. C. Doering, Angela Elliott, Paul and Erdmann, Jeanette Evans, David M. Falchi, Mario Feng, Wei Folsom, Aaron R. Frazer, Ian H. Gibson, Quince D. and Glazer, Nicole L. Hammond, Chris Hartikainen, Anna-Liisa and Heckbert, Susan R. Hengstenberg, Christian Hersch, Micha and Illig, Thomas Loos, Ruth J. F. Jolley, Jennifer Khaw, Kay Tee Kuehnel, Brigitte Kyrtsonis, Marie-Christine Lagou, Vasiliki Lloyd-Jones, Heather Lumley, Thomas Mangino, Massimo Maschio, Andrea Leach, Irene Mateo McKnight, Barbara and Memari, Yasin Mitchell, Braxton D. Montgomery, Grant W. and Nakamura, Yusuke Nauck, Matthias Navis, Gerjan Noethlings, Ute Nolte, Ilja M. Porteous, David J. Pouta, Anneli and Pramstaller, Peter P. Pullat, Janne Ring, Susan M. Rotter, Jerome I. Ruggiero, Daniela Ruokonen, Aimo Sala, Cinzia and Samani, Nilesh J. Sambrook, Jennifer Schlessinger, David and Schreiber, Stefan Schunkert, Heribert Scott, James Smith, Nicholas L. Snieder, Harold Starr, John M. Stumvoll, Michael and Takahashi, Atsushi Tang, W. H. Wilson Taylor, Kent and Tenesa, Albert Thein, Swee Lay Toenjes, Anke Uda, Manuela and Ulivi, Sheila van Veldhuisen, Dirk J. Visscher, Peter M. and Voelker, Uwe Wichmann, H-Erich Wiggins, Kerri L. Willemsen, Gonneke Yang, Tsun-Po Zhao, Jing Hua Zitting, Paavo and Bradley, John R. Dedoussis, George V. Gasparini, Paolo and Hazen, Stanley L. Metspalu, Andres Pirastu, Mario Shuldiner, Alan R. van Pelt, L. Joost Zwaginga, Jaap-Jan Boomsma, Dorret I. Deary, Ian J. Franke, Andre Froguel, Philippe and Ganesh, Santhi K. Jarvelin, Marjo-Riitta Martin, Nicholas G. and Meisinger, Christa Psaty, Bruce M. Spector, Timothy D. and Wareham, Nicholas J. Akkerman, Jan-Willem N. Ciullo, Marina and Deloukas, Panos Greinacher, Andreas Jupe, Steve Kamatani, Naoyuki Khadake, Jyoti Kooner, Jaspal S. Penninger, Josef and Prokopenko, Inga Stemple, Derek Toniolo, Daniela and Wernisch, Lorenz Sanna, Serena Hicks, Andrew A. Rendon, Augusto Ferreira, Manuel A. Ouwehand, Willem H. Soranzo, Nicole
- Abstract
Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.
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- 2011
37. Correction: Assessing Mitochondrial DNA Variation and Copy Number in Lymphocytes of ~2,000 Sardinians Using Tailored Sequencing Analysis Tools
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Ding, Jun, primary, Sidore, Carlo, additional, Butler, Thomas J., additional, Wing, Mary Kate, additional, Qian, Yong, additional, Meirelles, Osorio, additional, Busonero, Fabio, additional, Tsoi, Lam C., additional, Maschio, Andrea, additional, Angius, Andrea, additional, Kang, Hyun Min, additional, Nagaraja, Ramaiah, additional, Cucca, Francesco, additional, Abecasis, Gonçalo R., additional, and Schlessinger, David, additional
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- 2015
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38. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers
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Sidore, Carlo, primary, Busonero, Fabio, additional, Maschio, Andrea, additional, Porcu, Eleonora, additional, Naitza, Silvia, additional, Zoledziewska, Magdalena, additional, Mulas, Antonella, additional, Pistis, Giorgio, additional, Steri, Maristella, additional, Danjou, Fabrice, additional, Kwong, Alan, additional, Ortega del Vecchyo, Vicente Diego, additional, Chiang, Charleston W K, additional, Bragg-Gresham, Jennifer, additional, Pitzalis, Maristella, additional, Nagaraja, Ramaiah, additional, Tarrier, Brendan, additional, Brennan, Christine, additional, Uzzau, Sergio, additional, Fuchsberger, Christian, additional, Atzeni, Rossano, additional, Reinier, Frederic, additional, Berutti, Riccardo, additional, Huang, Jie, additional, Timpson, Nicholas J, additional, Toniolo, Daniela, additional, Gasparini, Paolo, additional, Malerba, Giovanni, additional, Dedoussis, George, additional, Zeggini, Eleftheria, additional, Soranzo, Nicole, additional, Jones, Chris, additional, Lyons, Robert, additional, Angius, Andrea, additional, Kang, Hyun M, additional, Novembre, John, additional, Sanna, Serena, additional, Schlessinger, David, additional, Cucca, Francesco, additional, and Abecasis, Gonçalo R, additional
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- 2015
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39. Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels
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Danjou, Fabrice, primary, Zoledziewska, Magdalena, additional, Sidore, Carlo, additional, Steri, Maristella, additional, Busonero, Fabio, additional, Maschio, Andrea, additional, Mulas, Antonella, additional, Perseu, Lucia, additional, Barella, Susanna, additional, Porcu, Eleonora, additional, Pistis, Giorgio, additional, Pitzalis, Maristella, additional, Pala, Mauro, additional, Menzel, Stephan, additional, Metrustry, Sarah, additional, Spector, Timothy D, additional, Leoni, Lidia, additional, Angius, Andrea, additional, Uda, Manuela, additional, Moi, Paolo, additional, Thein, Swee Lay, additional, Galanello, Renzo, additional, Abecasis, Gonçalo R, additional, Schlessinger, David, additional, Sanna, Serena, additional, and Cucca, Francesco, additional
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- 2015
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40. Assessing Mitochondrial DNA Variation and Copy Number in Lymphocytes of ~2,000 Sardinians Using Tailored Sequencing Analysis Tools
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Ding, Jun, primary, Sidore, Carlo, additional, Butler, Thomas J., additional, Wing, Mary Kate, additional, Qian, Yong, additional, Meirelles, Osorio, additional, Busonero, Fabio, additional, Tsoi, Lam C., additional, Maschio, Andrea, additional, Angius, Andrea, additional, Kang, Hyun Min, additional, Nagaraja, Ramaiah, additional, Cucca, Francesco, additional, Abecasis, Gonçalo R., additional, and Schlessinger, David, additional
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- 2015
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41. Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis
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Satta, Maria Anna, Maschio, Andrea, Zoledziewska, Magdalena, Poddie, Fausto, Pugliatti, Maura, Dei, Mariano, Sotgiu, Stefano, Ferrigno, Paola, Pitzalis, Maristella, Morelli, Laura, Liang, Liming, Sanna, Serena, Melis, Maria Cristina, Deidda, Francesca, Costa, Gianna, Zavattari, Patrizia, Deriu, Elisa, Porcu, Eleonora, Bajorek, Michele, Whalen, Michael B, Moi, Loredana, Lai, Sandra, Farina, Gabriele, Busonero, Fabio, Cocco, Eleonora, Cuccuru, Gianmauro, Mulas, Antonella, Sidore, Carlo, Urru, M Francesca, Zara, Ilenia, Li, Yun, and Murru, Raffaele
- Abstract
A genome wide association scan of ~6.6 million genotyped or imputed variants in 882 Sardinian Multiple Sclerosis (MS) cases and 872 controls suggested association of CBLB gene variants with disease, which was confirmed in 1,775 cases and 2,005 controls (overall P =1.60 × 10-10). CBLB encodes a negative regulator of adaptive immune responses and mice lacking the orthologue are prone to experimental autoimmune encephalomyelitis, the animal model of MS.
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- 2010
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42. Newly identified loci that influence lipid concentrations and risk of coronary artery disease
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Meneton, Pierre, Duren, William L, Scheet, Paul A, Heath, Simon C, Jackson, Anne U, Narisu, Narisu, Timpson, Nicholas J, Bonnycastle, Lori L, Maschio, Andrea, Busonero, Fabio, Shen, Haiqing, Clarke, Robert, Albai, Giuseppe, Chen, Wei-Min, Stringham, Heather M, Hercberg, Serge, Zelenika, Diana, Scuteri, Angelo, Strait, James, Scott, Laura J, Parish, Sarah, Bennett, Derrick, Morken, Mario A, Galan, Pilar, Watanabe, Richard M, Sundvall, Jouko, Najjar, Samer S, Li, Yun, Swift, Amy J, Sanna, Serena, Willer, Cristen J, and Mulas, Antonella
- Subjects
lipids (amino acids, peptides, and proteins) - Abstract
To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.
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- 2008
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43. Rare variant genotype imputation with thousands of study-specific whole-genome sequences: implications for cost-effective study designs
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Pistis, Giorgio, primary, Porcu, Eleonora, additional, Vrieze, Scott I, additional, Sidore, Carlo, additional, Steri, Maristella, additional, Danjou, Fabrice, additional, Busonero, Fabio, additional, Mulas, Antonella, additional, Zoledziewska, Magdalena, additional, Maschio, Andrea, additional, Brennan, Christine, additional, Lai, Sandra, additional, Miller, Michael B, additional, Marcelli, Marco, additional, Urru, Maria Francesca, additional, Pitzalis, Maristella, additional, Lyons, Robert H, additional, Kang, Hyun M, additional, Jones, Chris M, additional, Angius, Andrea, additional, Iacono, William G, additional, Schlessinger, David, additional, McGue, Matt, additional, Cucca, Francesco, additional, Abecasis, Gonçalo R, additional, and Sanna, Serena, additional
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- 2014
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44. Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits
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Randall, Joshua C., Winkler, Thomas W., Kutalik, Zoltan, Berndt, Sonja I., Jackson, Anne U., Monda, Keri L., Kilpelaeinen, Tuomas O., Esko, Tonu, Maegi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F., Croteau-Chonka, Damien C., Day, Felix R., Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E., Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R., Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T., Dimas, Antigone S., Karpe, Fredrik, Min, Josine L., Nicholson, George, Clegg, Deborah J., Person, Thomas, Krohn, Jon P., Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amelie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L., Harris, Tamara B., Smith, Albert Vernon, Shuldiner, Alan R., McArdle, Wendy L., Caulfield, Mark J., Munroe, Patricia B., Gronberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S., Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J., Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A., Kraja, Aldi T., Province, Michael A., Cupples, L. Adrienne, Heard-Costa, Nancy L., Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S., Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H. Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A., Johansson, Åsa, Pramstaller, Peter P., Kathiresan, Sekar, Speliotes, Elizabeth K., Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I., Campbell, Harry, Wilson, James F., Chanock, Stephen J., Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, Andre G., Hofman, Albert, Zillikens, M. Carola, den Heijer, Martin, Kiemeney, Lambertus A., Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Voelzke, Henry, Kovacs, Peter, Toenjes, Anke, Mangino, Massimo, Spector, Tim D., Hayward, Caroline, Rudan, Igor, Hall, Alistair S., Samani, Nilesh J., Attwood, Antony Paul, Sambrook, Jennifer G., Hung, Joseph, Palmer, Lyle J., Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G., Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M., Snieder, Harold, Van der Klauw, Melanie M., Van Vliet-Ostaptchouk, Jana V., Gejman, Pablo V., Shi, Jianxin, Jacobs, Kevin B., Wang, Zhaoming, Bakker, Stephan J. L., Leach, Irene Mateo, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Yang, Jian, Chasman, Daniel I., Ridker, Paul M., Rose, Lynda M., Lehtimaki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G., Hyppoenen, Elina, Power, Chris, Anderson, Denise, Beilby, John P., Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R., Schwarz, Peter E. H., Kristiansson, Kati, Perola, Markus, Lindstrom, Jaana, Swift, Amy J., Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A., Rauramaa, Rainer, Bolton, Jennifer L., Fowkes, Gerry, Fraser, Ross M., Price, Jackie F., Fischer, Krista, KrjutAikov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K., Chines, Peter S., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Edkins, Sarah, Franks, Paul W., Hallmans, Goran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N. A., Erbel, Raimund, Moebus, Susanne, Noethen, Markus M., Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E., Strawbridge, Rona J., Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Mueller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O., Kleber, Marcus E., Maerz, Winfried, Winkelmann, Bernhard R., Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W. G., Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K. E., Pedersen, Nancy L., Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L., Njolstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L., Barroso, Ine S., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Abecasis, Goncalo R., McCarthy, Mark I., Hirschhorn, Joel N., Qi, Lu, Loos, Ruth J. F., Lindgren, Cecilia M., North, Kari E., Heid, Iris M., Randall, Joshua C., Winkler, Thomas W., Kutalik, Zoltan, Berndt, Sonja I., Jackson, Anne U., Monda, Keri L., Kilpelaeinen, Tuomas O., Esko, Tonu, Maegi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F., Croteau-Chonka, Damien C., Day, Felix R., Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E., Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R., Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T., Dimas, Antigone S., Karpe, Fredrik, Min, Josine L., Nicholson, George, Clegg, Deborah J., Person, Thomas, Krohn, Jon P., Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amelie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L., Harris, Tamara B., Smith, Albert Vernon, Shuldiner, Alan R., McArdle, Wendy L., Caulfield, Mark J., Munroe, Patricia B., Gronberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S., Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J., Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A., Kraja, Aldi T., Province, Michael A., Cupples, L. Adrienne, Heard-Costa, Nancy L., Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S., Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H. Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A., Johansson, Åsa, Pramstaller, Peter P., Kathiresan, Sekar, Speliotes, Elizabeth K., Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I., Campbell, Harry, Wilson, James F., Chanock, Stephen J., Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, Andre G., Hofman, Albert, Zillikens, M. Carola, den Heijer, Martin, Kiemeney, Lambertus A., Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Voelzke, Henry, Kovacs, Peter, Toenjes, Anke, Mangino, Massimo, Spector, Tim D., Hayward, Caroline, Rudan, Igor, Hall, Alistair S., Samani, Nilesh J., Attwood, Antony Paul, Sambrook, Jennifer G., Hung, Joseph, Palmer, Lyle J., Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G., Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M., Snieder, Harold, Van der Klauw, Melanie M., Van Vliet-Ostaptchouk, Jana V., Gejman, Pablo V., Shi, Jianxin, Jacobs, Kevin B., Wang, Zhaoming, Bakker, Stephan J. L., Leach, Irene Mateo, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Yang, Jian, Chasman, Daniel I., Ridker, Paul M., Rose, Lynda M., Lehtimaki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G., Hyppoenen, Elina, Power, Chris, Anderson, Denise, Beilby, John P., Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R., Schwarz, Peter E. H., Kristiansson, Kati, Perola, Markus, Lindstrom, Jaana, Swift, Amy J., Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A., Rauramaa, Rainer, Bolton, Jennifer L., Fowkes, Gerry, Fraser, Ross M., Price, Jackie F., Fischer, Krista, KrjutAikov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K., Chines, Peter S., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Edkins, Sarah, Franks, Paul W., Hallmans, Goran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N. A., Erbel, Raimund, Moebus, Susanne, Noethen, Markus M., Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E., Strawbridge, Rona J., Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Mueller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O., Kleber, Marcus E., Maerz, Winfried, Winkelmann, Bernhard R., Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W. G., Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K. E., Pedersen, Nancy L., Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L., Njolstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L., Barroso, Ine S., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Abecasis, Goncalo R., McCarthy, Mark I., Hirschhorn, Joel N., Qi, Lu, Loos, Ruth J. F., Lindgren, Cecilia M., North, Kari E., and Heid, Iris M.
- Abstract
Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5x10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
- Published
- 2013
- Full Text
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45. Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits
- Author
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University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Samuli Olli Ripatti / Principal Investigator, University of Helsinki, Department of Public Health, University of Helsinki, Haartman Institute, University of Helsinki, Clinicum, University of Helsinki, Diabetes and Obesity Research Program, University of Helsinki, Department of Public Health (-2009), Randall, Joshua C., Winkler, Thomas W., Kutalik, Zoltan, Berndt, Sonja I., Jackson, Anne U., Monda, Keri L., Kilpelaeinen, Tuomas O., Esko, Tonu, Maegi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F., Croteau-Chonka, Damien C., Day, Felix R., Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E., Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R., Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T., Dimas, Antigone S., Karpe, Fredrik, Min, Josine L., Nicholson, George, Clegg, Deborah J., Person, Thomas, Krohn, Jon P., Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amelie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L., Harris, Tamara B., Smith, Albert Vernon, Shuldiner, Alan R., McArdle, Wendy L., Caulfield, Mark J., Munroe, Patricia B., Gronberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S., Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J., Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A., Kraja, Aldi T., Province, Michael A., Cupples, L. Adrienne, Heard-Costa, Nancy L., Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S., Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H. Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A., Johansson, Asa, Pramstaller, Peter P., Kathiresan, Sekar, Speliotes, Elizabeth K., Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I., Campbell, Harry, Wilson, James F., Chanock, Stephen J., Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, Andre G., Hofman, Albert, Zillikens, M. Carola, den Heijer, Martin, Kiemeney, Lambertus A., Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Voelzke, Henry, Kovacs, Peter, Toenjes, Anke, Mangino, Massimo, Spector, Tim D., Hayward, Caroline, Rudan, Igor, Hall, Alistair S., Samani, Nilesh J., Attwood, Antony Paul, Sambrook, Jennifer G., Hung, Joseph, Palmer, Lyle J., Lokki, Marja-Liisa, Sinisalo, Juha-Pekka, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G., Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M., Snieder, Harold, Van der Klauw, Melanie M., Van Vliet-Ostaptchouk, Jana V., Gejman, Pablo V., Shi, Jianxin, Jacobs, Kevin B., Wang, Zhaoming, Bakker, Stephan J. L., Leach, Irene Mateo, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Yang, Jian, Chasman, Daniel I., Ridker, Paul M., Rose, Lynda M., Lehtimaki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G., Hyppoenen, Elina, Power, Chris, Anderson, Denise, Beilby, John P., Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R., Schwarz, Peter E. H., Kristiansson, Kati, Perola, Markus, Lindstrom, Jaana, Swift, Amy J., Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A., Rauramaa, Rainer, Bolton, Jennifer L., Fowkes, Gerry, Fraser, Ross M., Price, Jackie F., Fischer, Krista, KrjutAikov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K., Chines, Peter S., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Edkins, Sarah, Franks, Paul W., Hallmans, Goran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N. A., Erbel, Raimund, Moebus, Susanne, Noethen, Markus M., Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E., Strawbridge, Rona J., Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Mueller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O., Kleber, Marcus E., Maerz, Winfried, Winkelmann, Bernhard R., Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W. G., Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K. E., Pedersen, Nancy L., Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L., Njolstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimäki, Mika, Kumari, Meena, Assimes, Themistocles L., Barroso, Ine S., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Abecasis, Goncalo R., McCarthy, Mark I., Hirschhorn, Joel N., Qi, Lu, Loos, Ruth J. F., Lindgren, Cecilia M., North, Kari E., Heid, Iris M., Consortium, DIAGRAM, Investigators, MAGIC, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Samuli Olli Ripatti / Principal Investigator, University of Helsinki, Department of Public Health, University of Helsinki, Haartman Institute, University of Helsinki, Clinicum, University of Helsinki, Diabetes and Obesity Research Program, University of Helsinki, Department of Public Health (-2009), Randall, Joshua C., Winkler, Thomas W., Kutalik, Zoltan, Berndt, Sonja I., Jackson, Anne U., Monda, Keri L., Kilpelaeinen, Tuomas O., Esko, Tonu, Maegi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F., Croteau-Chonka, Damien C., Day, Felix R., Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E., Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R., Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T., Dimas, Antigone S., Karpe, Fredrik, Min, Josine L., Nicholson, George, Clegg, Deborah J., Person, Thomas, Krohn, Jon P., Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amelie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L., Harris, Tamara B., Smith, Albert Vernon, Shuldiner, Alan R., McArdle, Wendy L., Caulfield, Mark J., Munroe, Patricia B., Gronberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S., Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J., Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A., Kraja, Aldi T., Province, Michael A., Cupples, L. Adrienne, Heard-Costa, Nancy L., Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S., Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H. Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A., Johansson, Asa, Pramstaller, Peter P., Kathiresan, Sekar, Speliotes, Elizabeth K., Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I., Campbell, Harry, Wilson, James F., Chanock, Stephen J., Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, Andre G., Hofman, Albert, Zillikens, M. Carola, den Heijer, Martin, Kiemeney, Lambertus A., Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Voelzke, Henry, Kovacs, Peter, Toenjes, Anke, Mangino, Massimo, Spector, Tim D., Hayward, Caroline, Rudan, Igor, Hall, Alistair S., Samani, Nilesh J., Attwood, Antony Paul, Sambrook, Jennifer G., Hung, Joseph, Palmer, Lyle J., Lokki, Marja-Liisa, Sinisalo, Juha-Pekka, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G., Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M., Snieder, Harold, Van der Klauw, Melanie M., Van Vliet-Ostaptchouk, Jana V., Gejman, Pablo V., Shi, Jianxin, Jacobs, Kevin B., Wang, Zhaoming, Bakker, Stephan J. L., Leach, Irene Mateo, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Yang, Jian, Chasman, Daniel I., Ridker, Paul M., Rose, Lynda M., Lehtimaki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G., Hyppoenen, Elina, Power, Chris, Anderson, Denise, Beilby, John P., Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R., Schwarz, Peter E. H., Kristiansson, Kati, Perola, Markus, Lindstrom, Jaana, Swift, Amy J., Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A., Rauramaa, Rainer, Bolton, Jennifer L., Fowkes, Gerry, Fraser, Ross M., Price, Jackie F., Fischer, Krista, KrjutAikov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K., Chines, Peter S., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Edkins, Sarah, Franks, Paul W., Hallmans, Goran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N. A., Erbel, Raimund, Moebus, Susanne, Noethen, Markus M., Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E., Strawbridge, Rona J., Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Mueller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O., Kleber, Marcus E., Maerz, Winfried, Winkelmann, Bernhard R., Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W. G., Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K. E., Pedersen, Nancy L., Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L., Njolstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimäki, Mika, Kumari, Meena, Assimes, Themistocles L., Barroso, Ine S., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Abecasis, Goncalo R., McCarthy, Mark I., Hirschhorn, Joel N., Qi, Lu, Loos, Ruth J. F., Lindgren, Cecilia M., North, Kari E., Heid, Iris M., Consortium, DIAGRAM, and Investigators, MAGIC
- Published
- 2013
46. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits
- Author
-
MAGIC Investigators, Randall, Joshua C., Winkler, Thomas W., Kutalik, Zoltán, I. Berndt, Sonja, Jackson, Anne U., Monda, Keri L., Kilpeläinen, Tuomas O., Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F., Croteau-Chonka, Damien C., Day, Felix R., Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E., Mathieson, Iain, Scherag, André, Vedantam, Sailaja, Wood, Andrew R., Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T., Dimas, Antigone S., Karpe, Fredrik, Min, Josine L., Nicholson, George, Clegg, Deborah J., Person, Thomas, Krohn, Jon P., Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L., Harris, Tamara B., Smith, Albert Vernon, Shuldiner, Alan R., McArdle, Wendy L., Caulfield, Mark J., Munroe, Patricia B., Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S., Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J., Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A., Kraja, Aldi T., Province, Michael A., Cupples, L. Adrienne, Heard-Costa, Nancy L., Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S., Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, Heinz Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A., Johansson, Åsa, Pramstaller, Peter P., Kathiresan, Sekar, Speliotes, Elizabeth K., Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I., Campbell, Harry, Wilson, James F., Chanock, Stephen J., Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G., Hofman, Albert, Zillikens, M. Carola, Heijer, Martin den, Kiemeney, Lambertus Adrianus, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D., Hayward, Caroline, Rudan, Igor, Hall, Alistair S., Samani, Nilesh J., Attwood, Antony Paul, Sambrook, Jennifer G., Hung, Joseph, Palmer, Lyle J., Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G., Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M., Snieder, Harold, Klauw, Melanie M. van der, Vliet-Ostaptchouk, Jana V. van, Gejman, Pablo V., Shi, Jianxin, Jacobs, Kevin B., Wang, Zhaoming, Bakker, Stephan J. L., Mateo Leach, Irene, Navis, Gerjan, Harst, Pim van der, Martin, Nicholas Gordon, Medland, Sarah E., Montgomery, Grant W., Yang, Jian, Chasman, Daniel I., Ridker, Paul M., Rose, Lynda M., Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G., Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P., Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R., Schwarz, Peter E. H., Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J., Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A., Rauramaa, Rainer, Bolton, Jennifer L., Fowkes, Gerry, Fraser, Ross M., Price, Jackie F., Fischer, Krista, KrjutÅ¡kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K., Chines, Peter S., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Edkins, Sarah, Franks, Paul W., Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N. A., Erbel, Raimund, Moebus, Susanne, Nöthen, Markus Maria, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E., Strawbridge, Rona J., Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Böhm, Bernhard O., Kleber, Marcus E., März, Winfried, Winkelmann, Bernhard R., Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W. G., Kuh, Diana, Wong, Andrew, Lind, Lars, Faire, Ulf de, Gigante, Bruna, Magnusson, Patrik K. E., Pedersen, Nancy L., Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L., Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L., Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L., North, Kari E., Lindgren, Cecilia M., Qi, Lu, Loos, Ruth J. F., Heid, Iris M., Hirschhorn, Joel N., McCarthy, Mark I., Abecasis, Gonçalo R., Stefansson, Kari, Strachan, David P., Schlessinger, David, O'Connell, Jeffrey R., Duijn, Cornelia M. van, MAGIC Investigators, Randall, Joshua C., Winkler, Thomas W., Kutalik, Zoltán, I. Berndt, Sonja, Jackson, Anne U., Monda, Keri L., Kilpeläinen, Tuomas O., Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F., Croteau-Chonka, Damien C., Day, Felix R., Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E., Mathieson, Iain, Scherag, André, Vedantam, Sailaja, Wood, Andrew R., Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T., Dimas, Antigone S., Karpe, Fredrik, Min, Josine L., Nicholson, George, Clegg, Deborah J., Person, Thomas, Krohn, Jon P., Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L., Harris, Tamara B., Smith, Albert Vernon, Shuldiner, Alan R., McArdle, Wendy L., Caulfield, Mark J., Munroe, Patricia B., Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S., Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J., Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A., Kraja, Aldi T., Province, Michael A., Cupples, L. Adrienne, Heard-Costa, Nancy L., Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S., Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, Heinz Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A., Johansson, Åsa, Pramstaller, Peter P., Kathiresan, Sekar, Speliotes, Elizabeth K., Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I., Campbell, Harry, Wilson, James F., Chanock, Stephen J., Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G., Hofman, Albert, Zillikens, M. Carola, Heijer, Martin den, Kiemeney, Lambertus Adrianus, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D., Hayward, Caroline, Rudan, Igor, Hall, Alistair S., Samani, Nilesh J., Attwood, Antony Paul, Sambrook, Jennifer G., Hung, Joseph, Palmer, Lyle J., Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G., Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M., Snieder, Harold, Klauw, Melanie M. van der, Vliet-Ostaptchouk, Jana V. van, Gejman, Pablo V., Shi, Jianxin, Jacobs, Kevin B., Wang, Zhaoming, Bakker, Stephan J. L., Mateo Leach, Irene, Navis, Gerjan, Harst, Pim van der, Martin, Nicholas Gordon, Medland, Sarah E., Montgomery, Grant W., Yang, Jian, Chasman, Daniel I., Ridker, Paul M., Rose, Lynda M., Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G., Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P., Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R., Schwarz, Peter E. H., Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J., Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A., Rauramaa, Rainer, Bolton, Jennifer L., Fowkes, Gerry, Fraser, Ross M., Price, Jackie F., Fischer, Krista, KrjutÅ¡kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K., Chines, Peter S., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Edkins, Sarah, Franks, Paul W., Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N. A., Erbel, Raimund, Moebus, Susanne, Nöthen, Markus Maria, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E., Strawbridge, Rona J., Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Böhm, Bernhard O., Kleber, Marcus E., März, Winfried, Winkelmann, Bernhard R., Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W. G., Kuh, Diana, Wong, Andrew, Lind, Lars, Faire, Ulf de, Gigante, Bruna, Magnusson, Patrik K. E., Pedersen, Nancy L., Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L., Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L., Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L., North, Kari E., Lindgren, Cecilia M., Qi, Lu, Loos, Ruth J. F., Heid, Iris M., Hirschhorn, Joel N., McCarthy, Mark I., Abecasis, Gonçalo R., Stefansson, Kari, Strachan, David P., Schlessinger, David, O'Connell, Jeffrey R., and Duijn, Cornelia M. van
- Abstract
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
- Published
- 2013
47. Exome-wide association study of plasma lipids in >300,000 individuals
- Author
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Liu, Dajiang J, Peloso, Gina M, Yu, Haojie, Butterworth, Adam S, Wang, Xiao, Mahajan, Anubha, Saleheen, Danish, Emdin, Connor, Alam, Dewan, Alves, Alexessander Couto, Amouyel, Philippe, Di Angelantonio, Emanuele, Arveiler, Dominique, Assimes, Themistocles L, Auer, Paul L, Baber, Usman, Ballantyne, Christie M, Bang, Lia E, Benn, Marianne, Bis, Joshua C, Boehnke, Michael, Boerwinkle, Eric, Bork-Jensen, Jette, Bottinger, Erwin P, Brandslund, Ivan, Brown, Morris, Busonero, Fabio, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Y Eugene, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Connell, John M, Cucca, Francesco, Cupples, L Adrienne, Damrauer, Scott M, Davies, Gail, Deary, Ian J, Dedoussis, George, Denny, Joshua C, Dominiczak, Anna, Dubé, Marie-Pierre, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Farmaki, Aliki-Eleni, Feitosa, Mary F, Ferrario, Marco, Ferrieres, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W, Frayling, Timothy M, Frikke-Schmidt, Ruth, Fritsche, Lars G, Frossard, Philippe, Fuster, Valentin, Ganesh, Santhi K, Gao, Wei, Garcia, Melissa E, Gieger, Christian, Giulianini, Franco, Goodarzi, Mark O, Grallert, Harald, Grarup, Niels, Groop, Leif, Grove, Megan L, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B, Hayward, Caroline, Hirschhorn, Joel N, Holmen, Oddgeir L, Huffman, Jennifer, Huo, Yong, Hveem, Kristian, Jabeen, Sehrish, Jackson, Anne U, Jakobsdottir, Johanna, Jarvelin, Marjo-Riitta, Jensen, Gorm B, Jørgensen, Marit E, Jukema, J Wouter, Justesen, Johanne M, Kamstrup, Pia R, Kanoni, Stavroula, Karpe, Fredrik, Kee, Frank, Khera, Amit V, Klarin, Derek, Koistinen, Heikki A, Kooner, Jaspal S, Kooperberg, Charles, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo, Langenberg, Claudia, Langsted, Anne, Launer, Lenore J, Lauritzen, Torsten, Liewald, David C M, Lin, Li An, Linneberg, Allan, Loos, Ruth J F, Lu, Yingchang, Lu, Xiangfeng, Mägi, Reedik, Malarstig, Anders, Manichaikul, Ani, Manning, Alisa K, Mäntyselkä, Pekka, Marouli, Eirini, Masca, Nicholas G D, Maschio, Andrea, Meigs, James B, Melander, Olle, Metspalu, Andres, Morris, Andrew P, Morrison, Alanna C, Mulas, Antonella, Müller-Nurasyid, Martina, Munroe, Patricia B, Neville, Matt J, Nielsen, Jonas B, Nielsen, Sune F, Nordestgaard, Børge G, Ordovas, Jose M, Mehran, Roxana, O'Donnell, Christoper J, Orho-Melander, Marju, Molony, Cliona M, Muntendam, Pieter, Padmanabhan, Sandosh, Palmer, Colin N A, Pasko, Dorota, Patel, Aniruddh P, Pedersen, Oluf, Perola, Markus, Peters, Annette, Pisinger, Charlotta, Pistis, Giorgio, Polasek, Ozren, Poulter, Neil, Psaty, Bruce M, Rader, Daniel J, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Reiner, Alex P, Renström, Frida, Rich, Stephen S, Ridker, Paul M, Rioux, John D, Robertson, Neil R, Roden, Dan M, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Sanna, Serena, Sattar, Naveed, Schmidt, Ellen M, Scott, Robert A, Sever, Peter, Sevilla, Raquel S, Shaffer, Christian M, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, Smith, Albert V, Smith, Blair H, Somayajula, Sangeetha, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Stirrups, Kathleen E, Stitziel, Nathan, Strauch, Konstantin, Stringham, Heather M, Surendran, Praveen, Tada, Hayato, Tall, Alan R, Tang, Hua, Tardif, Jean-Claude, Taylor, Kent D, Trompet, Stella, Tsao, Philip S, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, van Zuydam, Natalie R, Varbo, Anette, Varga, Tibor V, Virtamo, Jarmo, Waldenberger, Melanie, Wang, Nan, Wareham, Nick J, Warren, Helen R, Weeke, Peter E, Weinstock, Joshua, Wessel, Jennifer, Wilson, James G, Wilson, Peter W F, Xu, Ming, Yaghootkar, Hanieh, Young, Robin, Zeggini, Eleftheria, Zhang, He, Zheng, Neil S, Zhang, Weihua, Zhang, Yan, Zhou, Wei, Zhou, Yanhua, Zoledziewska, Magdalena, Howson, Joanna M M, Danesh, John, McCarthy, Mark I, Cowan, Chad A, Abecasis, Goncalo, Deloukas, Panos, Musunuru, Kiran, Willer, Cristen J, and Kathiresan, Sekar
- Abstract
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
- Published
- 2017
- Full Text
- View/download PDF
48. Hundreds of variants clustered in genomic loci and biological pathways affect human height
- Author
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Allen, Hana Lango, Estrada, Karol, Lettre, Guillaume, Berndt, Sonja I., Weedon, Michael N., Rivadeneira, Fernando, Willer, Cristen J., Jackson, Anne U., Vedantam, Sailaja, Raychaudhuri, Soumya, Ferreira, Teresa, Wood, Andrew R., Weyant, Robert J., Segre, Ayellet V., Speliotes, Elizabeth K., Wheeler, Eleanor, Soranzo, Nicole, Park, Ju-Hyun, Yang, Jian, Gudbjartsson, Daniel, Heard-Costa, Nancy L., Randall, Joshua C., Qi, Lu, Smith, Albert Vernon, Maegi, Reedik, Pastinen, Tomi, Liang, Liming, Heid, Iris M., Luan, Jian'an, Thorleifsson, Gudmar, Winkler, Thomas W., Goddard, Michael E., Lo, Ken Sin, Palmer, Cameron, Workalemahu, Tsegaselassie, Aulchenko, Yurii S., Johansson, Åsa, Zillikens, M. Carola, Feitosa, Mary F., Esko, Tonu, Johnson, Toby, Ketkar, Shamika, Kraft, Peter, Mangino, Massimo, Prokopenko, Inga, Absher, Devin, Albrecht, Eva, Ernst, Florian, Glazer, Nicole L., Hayward, Caroline, Hottenga, Jouke-Jan, Jacobs, Kevin B., Knowles, Joshua W., Kutalik, Zoltan, Monda, Keri L., Polasek, Ozren, Preuss, Michael, Rayner, Nigel W., Robertson, Neil R., Steinthorsdottir, Valgerdur, Tyrer, Jonathan P., Voight, Benjamin F., Wiklund, Fredrik, Xu, Jianfeng, Zhao, Jing Hua, Nyholt, Dale R., Pellikka, Niina, Perola, Markus, Perry, John R. B., Surakka, Ida, Tammesoo, Mari-Liis, Altmaier, Elizabeth L., Amin, Najaf, Aspelund, Thor, Bhangale, Tushar, Boucher, Gabrielle, Chasman, Daniel I., Chen, Constance, Coin, Lachlan, Cooper, Matthew N., Dixon, Anna L., Gibson, Quince, Grundberg, Elin, Hao, Ke, Junttila, M. Juhani, Kaplan, Lee M., Kettunen, Johannes, Koenig, Inke R., Kwan, Tony, Lawrence, Robert W., Levinson, Douglas F., Lorentzon, Mattias, McKnight, Barbara, Morris, Andrew P., Mueller, Martina, Ngwa, Julius Suh, Purcell, Shaun, Rafelt, Suzanne, Salem, Rany M., Salvi, Erika, Sanna, Serena, Shi, Jianxin, Sovio, Ulla, Thompson, John R., Turchin, Michael C., Vandenput, Liesbeth, Verlaan, Dominique J., Vitart, Veronique, White, Charles C., Ziegler, Andreas, Almgren, Peter, Balmforth, Anthony J., Campbell, Harry, Citterio, Lorena, De Grandi, Alessandro, Dominiczak, Anna, Duan, Jubao, Elliott, Paul, Elosua, Roberto, Eriksson, Johan G., Freimer, Nelson B., Geus, Eco J. C., Glorioso, Nicola, Haiqing, Shen, Hartikainen, Anna-Liisa, Havulinna, Aki S., Hicks, Andrew A., Hui, Jennie, Igl, Wilmar, Illig, Thomas, Jula, Antti, Kajantie, Eero, Kilpelaeinen, Tuomas O., Koiranen, Markku, Kolcic, Ivana, Koskinen, Seppo, Kovacs, Peter, Laitinen, Jaana, Liu, Jianjun, Lokki, Marja-Liisa, Marusic, Ana, Maschio, Andrea, Meitinger, Thomas, Mulas, Antonella, Pare, Guillaume, Parker, Alex N., Peden, John F., Petersmann, Astrid, Pichler, Irene, Pietilainen, Kirsi H., Pouta, Anneli, Riddertrale, Martin, Rotter, Jerome I., Sambrook, Jennifer G., Sanders, Alan R., Schmidt, Carsten Oliver, Sinisalo, Juha, Smit, Jan H., Stringham, Heather M., Walters, G. Bragi, Widen, Elisabeth, Wild, Sarah H., Willemsen, Gonneke, Zagato, Laura, Zgaga, Lina, Zitting, Paavo, Alavere, Helene, Farrall, Martin, McArdle, Wendy L., Nelis, Mari, Peters, Marjolein J., Ripatti, Samuli, vVan Meurs, Joyce B. J., Aben, Katja K., Ardlie, Kristin G., Beckmann, Jacques S., Beilby, John P., Bergman, Richard N., Bergmann, Sven, Collins, Francis S., Cusi, Daniele, den Heijer, Martin, Eiriksdottir, Gudny, Gejman, Pablo V., Hall, Alistair S., Hamsten, Anders, Huikuri, Heikki V., Iribarren, Carlos, Kahonen, Mika, Kaprio, Jaakko, Kathiresan, Sekar, Kiemeney, Lambertus, Kocher, Thomas, Launer, Lenore J., Lehtimaki, Terho, Melander, Olle, Mosley, Tom H., Jr., Musk, Arthur W., Nieminen, Markku S., O'Donnell, Christopher J., Ohlsson, Claes, Oostra, Ben, Palmer, Lyle J., Raitakari, Olli, Ridker, Paul M., Rioux, John D., Rissanen, Aila, Rivolta, Carlo, Schunkert, Heribert, Shuldiner, Alan R., Siscovick, David S., Stumvoll, Michael, Toenjes, Anke, Tuomilehto, Jaakko, van Ommen, Gert-Jan, Viikari, Jorma, Heath, Andrew C., Martin, Nicholas G., Montgomery, Grant W., Province, Michael A., Kayser, Manfred, Arnold, Alice M., Atwood, Larry D., Boerwinkle, Eric, Chanock, Stephen J., Deloukas, Panos, Gieger, Christian, Gronberg, Henrik, Hall, Per, Hattersley, Andrew T., Hengstenberg, Christian, Hoffman, Wolfgang, Lathrop, G. Mark, Salomaa, Veikko, Schreiber, Stefan, Uda, Manuela, Waterworth, Dawn, Wright, Alan F., Assimes, Themistocles L., Barroso, Ines, Hofman, Albert, Mohlke, Karen L., Boomsma, Dorret I., Caulfield, Mark J., Cupples, L. Adrienne, Erdmann, Jeanette, Fox, Caroline S., Gudnason, Vilmundur, Gyllensten, Ulf, Harris, Tamara B., Hayes, Richard B., Jarvelin, Marjo-Ritta, Mooser, Vincent, Munroe, Patricia B., Ouwehand, Willem H., Penninx, Brenda W., Pramstaller, Peter P., Quertermous, Thomas, Rudan, Igor, Samani, Nilesh J., Spector, Timothy D., Voelzke, Henry, Watkins, Hugh, Wilson, James F., Groop, Leif C., Haritunians, Talin, Hu, Frank B., Kaplan, Robert C., Metspalu, Andres, North, Kari E., Schlessinger, David, Wareham, Nicholas J., Hunter, David J., O'Connell, Jeffrey R., Strachan, David P., Schadt, H. -Erich, Thorsteinsdottir, Unnur, Peltonen, Leena, Uitterlinden, Andre G., Visscher, Peter M., Chatterjee, Nilanjan, Loos, Ruth J. F., Boehnke, Michael, McCarthy, Mark I., Ingelsson, Erik, Lindgren, Cecilia M., Abecasis, Goncalo R., Stefansson, Kari, Frayling, Timothy M., Hirschhorn, Joel N., Allen, Hana Lango, Estrada, Karol, Lettre, Guillaume, Berndt, Sonja I., Weedon, Michael N., Rivadeneira, Fernando, Willer, Cristen J., Jackson, Anne U., Vedantam, Sailaja, Raychaudhuri, Soumya, Ferreira, Teresa, Wood, Andrew R., Weyant, Robert J., Segre, Ayellet V., Speliotes, Elizabeth K., Wheeler, Eleanor, Soranzo, Nicole, Park, Ju-Hyun, Yang, Jian, Gudbjartsson, Daniel, Heard-Costa, Nancy L., Randall, Joshua C., Qi, Lu, Smith, Albert Vernon, Maegi, Reedik, Pastinen, Tomi, Liang, Liming, Heid, Iris M., Luan, Jian'an, Thorleifsson, Gudmar, Winkler, Thomas W., Goddard, Michael E., Lo, Ken Sin, Palmer, Cameron, Workalemahu, Tsegaselassie, Aulchenko, Yurii S., Johansson, Åsa, Zillikens, M. Carola, Feitosa, Mary F., Esko, Tonu, Johnson, Toby, Ketkar, Shamika, Kraft, Peter, Mangino, Massimo, Prokopenko, Inga, Absher, Devin, Albrecht, Eva, Ernst, Florian, Glazer, Nicole L., Hayward, Caroline, Hottenga, Jouke-Jan, Jacobs, Kevin B., Knowles, Joshua W., Kutalik, Zoltan, Monda, Keri L., Polasek, Ozren, Preuss, Michael, Rayner, Nigel W., Robertson, Neil R., Steinthorsdottir, Valgerdur, Tyrer, Jonathan P., Voight, Benjamin F., Wiklund, Fredrik, Xu, Jianfeng, Zhao, Jing Hua, Nyholt, Dale R., Pellikka, Niina, Perola, Markus, Perry, John R. B., Surakka, Ida, Tammesoo, Mari-Liis, Altmaier, Elizabeth L., Amin, Najaf, Aspelund, Thor, Bhangale, Tushar, Boucher, Gabrielle, Chasman, Daniel I., Chen, Constance, Coin, Lachlan, Cooper, Matthew N., Dixon, Anna L., Gibson, Quince, Grundberg, Elin, Hao, Ke, Junttila, M. Juhani, Kaplan, Lee M., Kettunen, Johannes, Koenig, Inke R., Kwan, Tony, Lawrence, Robert W., Levinson, Douglas F., Lorentzon, Mattias, McKnight, Barbara, Morris, Andrew P., Mueller, Martina, Ngwa, Julius Suh, Purcell, Shaun, Rafelt, Suzanne, Salem, Rany M., Salvi, Erika, Sanna, Serena, Shi, Jianxin, Sovio, Ulla, Thompson, John R., Turchin, Michael C., Vandenput, Liesbeth, Verlaan, Dominique J., Vitart, Veronique, White, Charles C., Ziegler, Andreas, Almgren, Peter, Balmforth, Anthony J., Campbell, Harry, Citterio, Lorena, De Grandi, Alessandro, Dominiczak, Anna, Duan, Jubao, Elliott, Paul, Elosua, Roberto, Eriksson, Johan G., Freimer, Nelson B., Geus, Eco J. C., Glorioso, Nicola, Haiqing, Shen, Hartikainen, Anna-Liisa, Havulinna, Aki S., Hicks, Andrew A., Hui, Jennie, Igl, Wilmar, Illig, Thomas, Jula, Antti, Kajantie, Eero, Kilpelaeinen, Tuomas O., Koiranen, Markku, Kolcic, Ivana, Koskinen, Seppo, Kovacs, Peter, Laitinen, Jaana, Liu, Jianjun, Lokki, Marja-Liisa, Marusic, Ana, Maschio, Andrea, Meitinger, Thomas, Mulas, Antonella, Pare, Guillaume, Parker, Alex N., Peden, John F., Petersmann, Astrid, Pichler, Irene, Pietilainen, Kirsi H., Pouta, Anneli, Riddertrale, Martin, Rotter, Jerome I., Sambrook, Jennifer G., Sanders, Alan R., Schmidt, Carsten Oliver, Sinisalo, Juha, Smit, Jan H., Stringham, Heather M., Walters, G. Bragi, Widen, Elisabeth, Wild, Sarah H., Willemsen, Gonneke, Zagato, Laura, Zgaga, Lina, Zitting, Paavo, Alavere, Helene, Farrall, Martin, McArdle, Wendy L., Nelis, Mari, Peters, Marjolein J., Ripatti, Samuli, vVan Meurs, Joyce B. J., Aben, Katja K., Ardlie, Kristin G., Beckmann, Jacques S., Beilby, John P., Bergman, Richard N., Bergmann, Sven, Collins, Francis S., Cusi, Daniele, den Heijer, Martin, Eiriksdottir, Gudny, Gejman, Pablo V., Hall, Alistair S., Hamsten, Anders, Huikuri, Heikki V., Iribarren, Carlos, Kahonen, Mika, Kaprio, Jaakko, Kathiresan, Sekar, Kiemeney, Lambertus, Kocher, Thomas, Launer, Lenore J., Lehtimaki, Terho, Melander, Olle, Mosley, Tom H., Jr., Musk, Arthur W., Nieminen, Markku S., O'Donnell, Christopher J., Ohlsson, Claes, Oostra, Ben, Palmer, Lyle J., Raitakari, Olli, Ridker, Paul M., Rioux, John D., Rissanen, Aila, Rivolta, Carlo, Schunkert, Heribert, Shuldiner, Alan R., Siscovick, David S., Stumvoll, Michael, Toenjes, Anke, Tuomilehto, Jaakko, van Ommen, Gert-Jan, Viikari, Jorma, Heath, Andrew C., Martin, Nicholas G., Montgomery, Grant W., Province, Michael A., Kayser, Manfred, Arnold, Alice M., Atwood, Larry D., Boerwinkle, Eric, Chanock, Stephen J., Deloukas, Panos, Gieger, Christian, Gronberg, Henrik, Hall, Per, Hattersley, Andrew T., Hengstenberg, Christian, Hoffman, Wolfgang, Lathrop, G. Mark, Salomaa, Veikko, Schreiber, Stefan, Uda, Manuela, Waterworth, Dawn, Wright, Alan F., Assimes, Themistocles L., Barroso, Ines, Hofman, Albert, Mohlke, Karen L., Boomsma, Dorret I., Caulfield, Mark J., Cupples, L. Adrienne, Erdmann, Jeanette, Fox, Caroline S., Gudnason, Vilmundur, Gyllensten, Ulf, Harris, Tamara B., Hayes, Richard B., Jarvelin, Marjo-Ritta, Mooser, Vincent, Munroe, Patricia B., Ouwehand, Willem H., Penninx, Brenda W., Pramstaller, Peter P., Quertermous, Thomas, Rudan, Igor, Samani, Nilesh J., Spector, Timothy D., Voelzke, Henry, Watkins, Hugh, Wilson, James F., Groop, Leif C., Haritunians, Talin, Hu, Frank B., Kaplan, Robert C., Metspalu, Andres, North, Kari E., Schlessinger, David, Wareham, Nicholas J., Hunter, David J., O'Connell, Jeffrey R., Strachan, David P., Schadt, H. -Erich, Thorsteinsdottir, Unnur, Peltonen, Leena, Uitterlinden, Andre G., Visscher, Peter M., Chatterjee, Nilanjan, Loos, Ruth J. F., Boehnke, Michael, McCarthy, Mark I., Ingelsson, Erik, Lindgren, Cecilia M., Abecasis, Goncalo R., Stefansson, Kari, Frayling, Timothy M., and Hirschhorn, Joel N.
- Abstract
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studie, Group Author(s): Procardis Consortium
- Published
- 2010
- Full Text
- View/download PDF
49. Genetic Variants Regulating Immune Cell Levels in Health and Disease
- Author
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Orrù, Valeria, primary, Steri, Maristella, additional, Sole, Gabriella, additional, Sidore, Carlo, additional, Virdis, Francesca, additional, Dei, Mariano, additional, Lai, Sandra, additional, Zoledziewska, Magdalena, additional, Busonero, Fabio, additional, Mulas, Antonella, additional, Floris, Matteo, additional, Mentzen, Wieslawa I., additional, Urru, Silvana A.M., additional, Olla, Stefania, additional, Marongiu, Michele, additional, Piras, Maria G., additional, Lobina, Monia, additional, Maschio, Andrea, additional, Pitzalis, Maristella, additional, Urru, Maria F., additional, Marcelli, Marco, additional, Cusano, Roberto, additional, Deidda, Francesca, additional, Serra, Valentina, additional, Oppo, Manuela, additional, Pilu, Rosella, additional, Reinier, Frederic, additional, Berutti, Riccardo, additional, Pireddu, Luca, additional, Zara, Ilenia, additional, Porcu, Eleonora, additional, Kwong, Alan, additional, Brennan, Christine, additional, Tarrier, Brendan, additional, Lyons, Robert, additional, Kang, Hyun M., additional, Uzzau, Sergio, additional, Atzeni, Rossano, additional, Valentini, Maria, additional, Firinu, Davide, additional, Leoni, Lidia, additional, Rotta, Gianluca, additional, Naitza, Silvia, additional, Angius, Andrea, additional, Congia, Mauro, additional, Whalen, Michael B., additional, Jones, Chris M., additional, Schlessinger, David, additional, Abecasis, Gonçalo R., additional, Fiorillo, Edoardo, additional, Sanna, Serena, additional, and Cucca, Francesco, additional
- Published
- 2013
- Full Text
- View/download PDF
50. A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation
- Author
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Naitza, Silvia, primary, Porcu, Eleonora, additional, Steri, Maristella, additional, Taub, Dennis D., additional, Mulas, Antonella, additional, Xiao, Xiang, additional, Strait, James, additional, Dei, Mariano, additional, Lai, Sandra, additional, Busonero, Fabio, additional, Maschio, Andrea, additional, Usala, Gianluca, additional, Zoledziewska, Magdalena, additional, Sidore, Carlo, additional, Zara, Ilenia, additional, Pitzalis, Maristella, additional, Loi, Alessia, additional, Virdis, Francesca, additional, Piras, Roberta, additional, Deidda, Francesca, additional, Whalen, Michael B., additional, Crisponi, Laura, additional, Concas, Antonio, additional, Podda, Carlo, additional, Uzzau, Sergio, additional, Scheet, Paul, additional, Longo, Dan L., additional, Lakatta, Edward, additional, Abecasis, Gonçalo R., additional, Cao, Antonio, additional, Schlessinger, David, additional, Uda, Manuela, additional, Sanna, Serena, additional, and Cucca, Francesco, additional
- Published
- 2012
- Full Text
- View/download PDF
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