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5 results on '"Heilmann, S."'

1. Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

Author

Webb, T.R., Erdmann, J., Stirrups, K.E., Stitziel, N.O., Masca, N.G.D., Jansen, H., Kanoni, S., Nelson, C.P., Ferrario, P.G., Konig, I.R., Eicher, J.D., Johnson, A.D., Hamby, S.E., Betsholtz, C., Ruusalepp, A., Franzen, O., Schadt, E.E., Bjorkegren, J.L.M., Weeke, P.E., Auer, P.L., Schick, U.M., Lu, Y.C., Zhang, H., Dube, M.P., Goel, A., Farrall, M., Peloso, G.M., Won, H.H., R. do, Iperen, E. van, Kruppa, J., Mahajan, A., Scott, R.A., Willenborg, C., Braund, P.S., Capelleveen, J.C. van, Doney, A.S.F., Donnelly, L.A., Asselta, R., Merlini, P.A., Duga, S., Marziliano, N., Denny, J.C., Shaffer, C., El-Mokhtari, N.E., Franke, A., Heilmann, S., Hengstenberg, C., Hoffmann, P., Holmen, O.L., Hveem, K., Jansson, J.H., Jockel, K.H., Kessler, T., Kriebel, J., Laugwitz, K.L., Marouli, E., Martinelli, N., McCarthy, M.I., Zuydam, N.R. van, Meisinger, C., Esko, T., Mihailov, E., Escher, S.A., Alver, M., Moebus, S., Morris, A.D., Virtamo, J., Nikpay, M., Olivieri, O., Provost, S., AlQarawi, A., Robertson, N.R., Akinsansya, K.O., Reilly, D.F., Vogt, T.F., Yin, W., Asselbergs, F.W., Kooperberg, C., Jackson, R.D., Stahl, E., Muller-Nurasyid, M., Strauch, K., Varga, T.V., Waldenberger, M., Zeng, L.Y., Chowdhury, R., Salomaa, V., Ford, I., Jukema, J.W., Amouyel, P., Kontto, J., Nordestgaard, B.G., Ferrieres, J., Saleheen, D., Sattar, N., Surendran, P., Wagner, A., Young, R., Howson, J.M.M., Butterworth, A.S., Danesh, J., Ardissino, D., Bottinger, E.P., Erbel, R., Franks, P.W., Girelli, D., Hall, A.S., Hovingh, G.K., Kastrati, A., Lieb, W., Meitinger, T., Kraus, W.E., Shah, S.H., McPherson, R., Orho-Melander, M., Melander, O., Metspalu, A., Palmer, C.N.A., Peters, A., Rader, D.J., Reilly, M.P., Loos, R.J.F., Reiner, A.P., Roden, D.M., Tardif, J.C., Thompson, J.R., Wareham, N.J., Watkins, H., Willer, C.J., Samani, N.J., Schunkert, H., Deloukas, P., Kathiresan, S., Wellcome Trust Case Control, MORGAM Investigators, and Myocardial Infarction Genetics

Subjects
expression quantitative trait loci, single nucleotide polymorphism, cholesteryl ester transfer protein, genome-wide association, genetics
Abstract

BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10(-4) with a range of other diseases/traits. CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.

Published
2017

2. No genetic support for a contribution of prostaglandins to the aetiology of androgenetic alopecia

Author

Heilmann, S., Nyholt, D. R., Bataille, V., Brockschmidt, F. F., Dedoussis, G., Deloukas, P., den Heijer, M., Dimitriou, M., Eigelshoven, S., Eriksson, N., Geller, F., Glass, D., Hanneken, S., Heath, A. C., Hillmer, A. M., Hinds, D. A., Kanoni, S., Kárason, A., Kiefer, A. K., Kiemeney, L. A., Li, R., Mangino, M., Martin, N. G., Medland, S. E., Moebus, S., Montgomery, G. W., Mooser, V., Richards, J. B., Song, K., Spector, T. D., Herold, C., Stefansson, H., Stefansson, K., Sulem, P., Tung, J. Y., Vermeulen, S. H., Vollenweider, P., Waterworth, D., Consortium, Maan, Becker, T., Nöthen, M. M., and Consortium, Meta-Analysis for Androgenetic Alopecia Novel Determinants

Subjects
Candidate gene, Receptors, Prostaglandin, Genome-wide association study, Aetiology, screening and detection [ONCOL 5], Dermatology, Disease, Biology, Molecular epidemiology [NCEBP 1], Genetic predisposition, medicine, genetics [Receptors, Immunologic], Humans, ddc:610, Receptors, Immunologic, genetics [Alopecia], Molecular epidemiology Aetiology, screening and detection [NCEBP 1], Genetic association, genetics [Prostaglandin D2], Genetics, Prostaglandin D2, Alopecia, medicine.disease, Phenotype, genetics [Receptors, Prostaglandin], Hair loss, metabolism [Prostaglandin D2], Trait, prostaglandin D2 receptor
Abstract

MADAM, Androgenetic alopecia (AGA) is a common age-dependent trait, characterized by a progressive loss of hair from the scalp. The hair loss may commence during puberty and up to 80% of white men experience some degree of AGA during their lifetime.1 Research has established that two essential aetiological factors for AGA are a genetic predisposition and the presence of androgens (male sex hormones).1,2 A recent meta-analysis of genome-wide association studies (GWAS) has increased the number of identified loci associated with this trait at the molecular level to a total of eight.3 However, despite these successes, a large fraction of the genetic contribution remains to be identified. One way to identify further genetic loci is to combine the resource of GWAS datasets with knowledge about specific biological factors likely to be involved in the development of disease. The focused evaluation of a limited number of candidate genes in GWAS datasets avoids the necessity for extensive correction for multiple testing, which typically limits the power for detecting genetic loci at a genome-wide level.4 Because the presence of genetic association suggests that candidate genes are likely to operate early in the causative chain of events leading to the phenotype, this approach may also function to favour biological pathways for their importance in the development of AGA.

Published
2013
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3. Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene

Author

Ruiz, A., Heilmann, S., Harold, D., Gerrish, A., Sims, R., Sotolongo-Grau, O., Espinosa, A., Alegret, M., Arrieta, J. L., Lacour, A., Leber, M., Becker, J., Becker, T., Lafuente, A., Ruiz, S., Vargas, L., Rodríguez, O., Ortega, G., Dominguez, M-A, IGAP, Mayeux, R., Haines, J. L., Pericak-Vance, M. A., Hernández, I., Farrer, L. A., Schellenberg, G. D., Chouraki, V., Launer, L. J., van Duijn, C., Seshadri, S., Antúnez, C., Breteler, Monique, Serrano-Ríos, M., Jessen, F., Wagner, H., Tárraga, L., Nöthen, M. M., Maier, W., Boada, M., Ramírez, A., Thelen, M., Mauleón, A., Rosende-Roca, M., Bellenguez, C., Bis, J. C., Breteler, M. M., and Epidemiology

Subjects
SNP, thyroid receptor, Genomics, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, genetics [Alzheimer Disease], TRIP4 protein, human, genetics [Genetic Loci], Biology, Polymorphism, Single Nucleotide, molecular epidemiology, Cellular and Molecular Neuroscience, Alzheimer Disease, dementia risk, medicine, GWAS, Humans, Genetic Predisposition to Disease, ddc:610, Biological Psychiatry, Genetics, Odds ratio, DNA, genetics [Transcription Factors], medicine.disease, R1, Psychiatry and Mental health, Genetic Loci, Spain, Multiple comparisons problem, genetics [Polymorphism, Single Nucleotide], Original Article, Alzheimer's disease, Follow-Up Studies, Genome-Wide Association Study, Transcription Factors
Abstract

To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundacio ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P = 0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio = 1.31; confidence interval 95% (1.19-1.44); P = 9.74 x 10(-9)).

Published
2014
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4. Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness.

Author

Brockschmidt, F.F., Heilmann, S., Ellis, J.A., Eigelshoven, S., Hanneken, S., Herold, C., Moebus, S., Alblas, M.A., Lippke, B., Kluck, N., Priebe, L., Degenhardt, F.A., Jamra, R.A., Meesters, C., Jöckel, K.-H., Erbel, R., Harrap, S., Schumacher, J., Fröhlich, H., and Kruse, R.

Subjects
*BALDNESS, *CHROMOSOMES, *HISTONE deacetylase, *ANDROGENS, *REVERSE transcriptase polymerase chain reaction, *GENETICS
Abstract

Summary Background Male-pattern baldness (androgenetic alopecia, AGA) is the most common form of hair loss among humans. Research has shown that it is caused by genetic factors. Numerous studies have unequivocally identified two major genetic risk loci for AGA: the X-chromosomal AR/ EDA2R locus, and the PAX1/ FOXA2 locus on chromosome 20. Objectives To identify further candidate genes for AGA, and thus gain further insights into this phenotype. Methods A German sample of 581 severely affected cases and 617 controls was used to perform a genome-wide association study. The identified associated locus was further analysed by fine-mapping, and then independently replicated in an Australian sample. Expression and pathway analyses were performed to characterize the susceptibility gene identified. Results The most significant association signal was obtained for rs756853 ( P = 1·64 × 10−7), which is located intronically in the histone deacetylase 9 ( HDAC9) gene. Fine-mapping and a family-based analysis revealed that rs756853 and the 6-kb distal rs2249817 were the most highly associated single nucleotide polymorphisms. The association finding was replicated in an independent Australian sample, when the analysis was restricted to severely affected cases and unaffected controls ( P = 0·026). Analysis of rs2249817 in a combined sample of severely affected German and Australian cases and unaffected controls revealed a strong association signal ( P = 9·09 × 10−8). Tissue expression studies demonstrated HDAC9 expression in various tissues, including tissues of relevance to AGA. No strong genotypic effects were observed in genotype-specific expression or splice studies. Pathway analyses supported the hypothesis that HDAC9 plays a functional role in AGA via interaction with the AR gene. Conclusions The present study suggests that HDAC9 is the third AGA susceptibility gene. [ABSTRACT FROM AUTHOR]

Published
2011
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5. Systematic evaluation of pleiotropy identifies 6 further loci associated with coronary artery disease

Author

Webb, T, Erdmann, J, Stirrups, K, Stitziel, N, Masca, N, Jansen, H, Kanoni, S, Nelson, C, Ferrario, P, König, I, Eicher, J, Johnson, A, Hamby, S, Betsholtz, C, Ruusalepp, A, Franzén, O, Schadt, E, Björkegren, J, Weeke, P, Auer, P, Schick, U, Lu, Y, Zhang, H, Dube, M, Goel, A, Farrall, M, Peloso, G, Won, H, Do, R, van Iperen, E, Kruppa, J, Mahajan, A, Scott, R, Willenborg, C, Braund, P, van Capelleveen, J, Doney, A, Donnelly, L, Asselta, R, Merlini, P, Duga, S, Marziliano, N, Denny, J, Shaffer, C, El-Mokhtari, N, Franke, A, Heilmann, S, Hengstenberg, C, Hoffmann, P, Holmen, O, Hveem, K, Jansson, J, Jöckel, K, Kessler, T, Kriebel, J, Laugwitz, K, Marouli, E, Martinelli, N, McCarthy, M, Van Zuydam, N, Meisinger, C, Esko, T, Mihailov, E, Escher, S, Alver, M, Moebus, S, Morris, A, Virtamo, J, Nikpay, M, Olivieri, O, Provost, S, AlQarawi, A, Robertson, N, Akinsansya, K, Reilly, D, Vogt, T, Yin, W, Asselbergs, F, Kooperberg, C, Jackson, R, Stahl, E, Müller-Nurasyid, M, Strauch, K, Varga, T, Waldenberger, M, Consortium, Wellcome Trust Case Control, Zeng, L, Chowdhury, R, Salomaa, V, Ford, I, Jukema, J, Amouyel, P, Kontto, J, Investigators, MORGAM, Nordestgaard, B, Ferrières, J, Saleheen, D, Sattar, N, Surendran, P, Wagner, A, Young, R, Howson, J, Butterworth, A, Danesh, J, Ardissino, D, Bottinger, E, Erbel, R, Franks, P, Girelli, D, Hall, A, Hovingh, G, Kastrati, A, Lieb, W, Meitinger, T, Kraus, W, Shah, S, McPherson, R, Orho-Melander, M, Melander, O, Metspalu, A, Palmer, C, Peters, A, Rader, D, Reilly, M, Loos, R, Reiner, A, Roden, D, Tardif, J, Thompson, J, Wareham, N, Watkins, H, Willer, C, Samani, N, Schunkert, H, Deloukas, P, Kathiresan, S, Investigators, Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia, Johnson, Kathleen [0000-0002-6823-3252], Chowdhury, Rajiv [0000-0003-4881-5690], Surendran, Praveen [0000-0002-4911-6077], Howson, Joanna [0000-0001-7618-0050], Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository

Subjects
expression quantitative trait loci, single nucleotide polymorphism, cholesteryl ester transfer protein, genome-wide association, genetics
Abstract

BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10(-4) with a range of other diseases/traits. CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.

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