17 results on '"Murabito, J.M."'
Search Results
2. Angina pectoris is a stronger indicator of diffuse vascular atherosclerosis than intermittent claudication: Framingham study
- Author
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Kannel, W.B., Evans, J.C., Piper, S., and Murabito, J.M.
- Published
- 2008
- Full Text
- View/download PDF
3. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.
- Author
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McCartney D.L., Min J.L., Richmond R.C., Lu A.T., Sobczyk M.K., Davies G., Broer L., Guo X., Jeong A., Jung J., Kasela S., Katrinli S., Kuo P.-L., Matias-Garcia P.R., Mishra P.P., Nygaard M., Palviainen T., Patki A., Raffield L.M., Ratliff S.M., Richardson T.G., Robinson O., Soerensen M., Sun D., Tsai P.-C., van der Zee M.D., Walker R.M., Wang X., Wang Y., Xia R., Xu Z., Yao J., Zhao W., Correa A., Boerwinkle E., Dugue P.-A., Durda P., Elliott H.R., Gieger C., de Geus E.J.C., Harris S.E., Hemani G., Imboden M., Kahonen M., Kardia S.L.R., Kresovich J.K., Li S., Lunetta K.L., Mangino M., Mason D., McIntosh A.M., Mengel-From J., Moore A.Z., Murabito J.M., Ollikainen M., Pankow J.S., Pedersen N.L., Peters A., Polidoro S., Porteous D.J., Raitakari O., Rich S.S., Sandler D.P., Sillanpaa E., Smith A.K., Southey M.C., Strauch K., Tiwari H., Tanaka T., Tillin T., Uitterlinden A.G., Van Den Berg D.J., van Dongen J., Wilson J.G., Wright J., Yet I., Arnett D., Bandinelli S., Bell J.T., Binder A.M., Boomsma D.I., Chen W., Christensen K., Conneely K.N., Elliott P., Ferrucci L., Fornage M., Hagg S., Hayward C., Irvin M., Kaprio J., Lawlor D.A., Lehtimaki T., Lohoff F.W., Milani L., Milne R.L., Probst-Hensch N., Reiner A.P., Ritz B., Rotter J.I., Smith J.A., Taylor J.A., van Meurs J.B.J., Vineis P., Waldenberger M., Deary I.J., Relton C.L., Horvath S., Marioni R.E., McCartney D.L., Min J.L., Richmond R.C., Lu A.T., Sobczyk M.K., Davies G., Broer L., Guo X., Jeong A., Jung J., Kasela S., Katrinli S., Kuo P.-L., Matias-Garcia P.R., Mishra P.P., Nygaard M., Palviainen T., Patki A., Raffield L.M., Ratliff S.M., Richardson T.G., Robinson O., Soerensen M., Sun D., Tsai P.-C., van der Zee M.D., Walker R.M., Wang X., Wang Y., Xia R., Xu Z., Yao J., Zhao W., Correa A., Boerwinkle E., Dugue P.-A., Durda P., Elliott H.R., Gieger C., de Geus E.J.C., Harris S.E., Hemani G., Imboden M., Kahonen M., Kardia S.L.R., Kresovich J.K., Li S., Lunetta K.L., Mangino M., Mason D., McIntosh A.M., Mengel-From J., Moore A.Z., Murabito J.M., Ollikainen M., Pankow J.S., Pedersen N.L., Peters A., Polidoro S., Porteous D.J., Raitakari O., Rich S.S., Sandler D.P., Sillanpaa E., Smith A.K., Southey M.C., Strauch K., Tiwari H., Tanaka T., Tillin T., Uitterlinden A.G., Van Den Berg D.J., van Dongen J., Wilson J.G., Wright J., Yet I., Arnett D., Bandinelli S., Bell J.T., Binder A.M., Boomsma D.I., Chen W., Christensen K., Conneely K.N., Elliott P., Ferrucci L., Fornage M., Hagg S., Hayward C., Irvin M., Kaprio J., Lawlor D.A., Lehtimaki T., Lohoff F.W., Milani L., Milne R.L., Probst-Hensch N., Reiner A.P., Ritz B., Rotter J.I., Smith J.A., Taylor J.A., van Meurs J.B.J., Vineis P., Waldenberger M., Deary I.J., Relton C.L., Horvath S., and Marioni R.E.
- Abstract
Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Result(s): Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion(s): This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Copyright © 2021, The Author(s).
- Published
- 2021
4. Genetic insights into biological mechanisms governing human ovarian ageing.
- Author
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Ruth K.S., Day F.R., Hussain J., Martinez-Marchal A., Aiken C.E., Azad A., Thompson D.J., Knoblochova L., Abe H., Tarry-Adkins J.L., Gonzalez J.M., Fontanillas P., Claringbould A., Bakker O.B., Sulem P., Walters R.G., Terao C., Turon S., Horikoshi M., Lin K., Onland-Moret N.C., Sankar A., Hertz E.P.T., Timshel P.N., Shukla V., Borup R., Olsen K.W., Aguilera P., Ferrer-Roda M., Huang Y., Stankovic S., Timmers P.R.H.J., Ahearn T.U., Alizadeh B.Z., Naderi E., Andrulis I.L., Arnold A.M., Aronson K.J., Augustinsson A., Bandinelli S., Barbieri C.M., Beaumont R.N., Becher H., Beckmann M.W., Benonisdottir S., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Boomsma D.I., Bowker N., Brody J.A., Broer L., Buring J.E., Campbell A., Campbell H., Castelao J.E., Catamo E., Chanock S.J., Chenevix-Trench G., Ciullo M., Corre T., Couch F.J., Cox A., Crisponi L., Cross S.S., Cucca F., Czene K., Smith G.D., de Geus E.J.C.N., de Mutsert R., De Vivo I., Demerath E.W., Dennis J., Dunning A.M., Dwek M., Eriksson M., Esko T., Fasching P.A., Faul J.D., Ferrucci L., Franceschini N., Frayling T.M., Gago-Dominguez M., Mezzavilla M., Garcia-Closas M., Gieger C., Giles G.G., Grallert H., Gudbjartsson D.F., Gudnason V., Guenel P., Haiman C.A., Hakansson N., Hall P., Hayward C., He C., He W., Heiss G., Hoffding M.K., Hopper J.L., Hottenga J.J., Hu F., Hunter D., Ikram M.A., Jackson R.D., Joaquim M.D.R., John E.M., Joshi P.K., Karasik D., Kardia S.L.R., Kartsonaki C., Karlsson R., Kitahara C.M., Kolcic I., Kooperberg C., Kraft P., Kurian A.W., Kutalik Z., La Bianca M., LaChance G., Langenberg C., Launer L.J., Laven J.S.E., Lawlor D.A., Le Marchand L., Li J., Lindblom A., Lindstrom S., Lindstrom T., Linet M., Liu Y.M., Liu S., Luan J., Magi R., Magnusson P.K.E., Mangino M., Mannermaa A., Marco B., Marten J., Martin N.G., Mbarek H., McKnight B., Medland S.E., Meisinger C., Meitinger T., Menni C., Metspalu A., Milani L., Milne R.L., Montgomery G.W., Mook-Kanamori D.O., Mulas A., Mulligan A.M., Nalls M.A., Newman A., Noordam R., Nutile T., Nyholt D.R., Olshan A.F., Olsson H., Painter J.N., Patel A.V., Pedersen N.L., Perjakova N., Peters A., Peters U., Pharoah P.D.P., Polasek O., Porcu E., Psaty B.M., Rahman I., Rennert G., Rennert H.S., Ridker P.M., Ring S.M., Robino A., Rose L.M., Rosendaal F.R., Rossouw J., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Saloustros E., Sandler D.P., Sanna S., Sawyer E.J., Sarnowski C., Schlessinger D., Schmidt M.K., Schoemaker M.J., Schraut K.E., Scott C., Shekari S., Shrikhande A., Smith A.V., Smith B.H., Smith J.A., Sorice R., Southey M.C., Spector T.D., Spinelli J.J., Stampfer M., Stockl D., van Meurs J.B.J., Strauch K., Styrkarsdottir U., Swerdlow A.J., Tanaka T., Teras L.R., Teumer A., Thorsteinsdottir U., Timpson N.J., Toniolo D., Traglia M., Troester M.A., Truong T., Tyrrell J., Uitterlinden A.G., Ulivi S., Vachon C.M., Vitart V., Volker U., Vollenweider P., Volzke H., Wang Q., Wareham N.J., Weinberg C.R., Weir D.R., Wilcox A.N., van Dijk K.W., Willemsen G., Wilson J.F., Wolffenbuttel B.H.R., Wolk A., Wood A.R., Zhao W., Zygmunt M., Chen Z., Li L., Franke L., Burgess S., Deelen P., Pers T.H., Grondahl M.L., Andersen C.Y., Pujol A., Lopez-Contreras A.J., Daniel J.A., Stefansson K., Chang-Claude J., van der Schouw Y.T., Lunetta K.L., Chasman D.I., Easton D.F., Visser J.A., Ozanne S.E., Namekawa S.H., Solc P., Murabito J.M., Ong K.K., Hoffmann E.R., Murray A., Roig I., Perry J.R.B., Ruth K.S., Day F.R., Hussain J., Martinez-Marchal A., Aiken C.E., Azad A., Thompson D.J., Knoblochova L., Abe H., Tarry-Adkins J.L., Gonzalez J.M., Fontanillas P., Claringbould A., Bakker O.B., Sulem P., Walters R.G., Terao C., Turon S., Horikoshi M., Lin K., Onland-Moret N.C., Sankar A., Hertz E.P.T., Timshel P.N., Shukla V., Borup R., Olsen K.W., Aguilera P., Ferrer-Roda M., Huang Y., Stankovic S., Timmers P.R.H.J., Ahearn T.U., Alizadeh B.Z., Naderi E., Andrulis I.L., Arnold A.M., Aronson K.J., Augustinsson A., Bandinelli S., Barbieri C.M., Beaumont R.N., Becher H., Beckmann M.W., Benonisdottir S., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Boomsma D.I., Bowker N., Brody J.A., Broer L., Buring J.E., Campbell A., Campbell H., Castelao J.E., Catamo E., Chanock S.J., Chenevix-Trench G., Ciullo M., Corre T., Couch F.J., Cox A., Crisponi L., Cross S.S., Cucca F., Czene K., Smith G.D., de Geus E.J.C.N., de Mutsert R., De Vivo I., Demerath E.W., Dennis J., Dunning A.M., Dwek M., Eriksson M., Esko T., Fasching P.A., Faul J.D., Ferrucci L., Franceschini N., Frayling T.M., Gago-Dominguez M., Mezzavilla M., Garcia-Closas M., Gieger C., Giles G.G., Grallert H., Gudbjartsson D.F., Gudnason V., Guenel P., Haiman C.A., Hakansson N., Hall P., Hayward C., He C., He W., Heiss G., Hoffding M.K., Hopper J.L., Hottenga J.J., Hu F., Hunter D., Ikram M.A., Jackson R.D., Joaquim M.D.R., John E.M., Joshi P.K., Karasik D., Kardia S.L.R., Kartsonaki C., Karlsson R., Kitahara C.M., Kolcic I., Kooperberg C., Kraft P., Kurian A.W., Kutalik Z., La Bianca M., LaChance G., Langenberg C., Launer L.J., Laven J.S.E., Lawlor D.A., Le Marchand L., Li J., Lindblom A., Lindstrom S., Lindstrom T., Linet M., Liu Y.M., Liu S., Luan J., Magi R., Magnusson P.K.E., Mangino M., Mannermaa A., Marco B., Marten J., Martin N.G., Mbarek H., McKnight B., Medland S.E., Meisinger C., Meitinger T., Menni C., Metspalu A., Milani L., Milne R.L., Montgomery G.W., Mook-Kanamori D.O., Mulas A., Mulligan A.M., Nalls M.A., Newman A., Noordam R., Nutile T., Nyholt D.R., Olshan A.F., Olsson H., Painter J.N., Patel A.V., Pedersen N.L., Perjakova N., Peters A., Peters U., Pharoah P.D.P., Polasek O., Porcu E., Psaty B.M., Rahman I., Rennert G., Rennert H.S., Ridker P.M., Ring S.M., Robino A., Rose L.M., Rosendaal F.R., Rossouw J., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Saloustros E., Sandler D.P., Sanna S., Sawyer E.J., Sarnowski C., Schlessinger D., Schmidt M.K., Schoemaker M.J., Schraut K.E., Scott C., Shekari S., Shrikhande A., Smith A.V., Smith B.H., Smith J.A., Sorice R., Southey M.C., Spector T.D., Spinelli J.J., Stampfer M., Stockl D., van Meurs J.B.J., Strauch K., Styrkarsdottir U., Swerdlow A.J., Tanaka T., Teras L.R., Teumer A., Thorsteinsdottir U., Timpson N.J., Toniolo D., Traglia M., Troester M.A., Truong T., Tyrrell J., Uitterlinden A.G., Ulivi S., Vachon C.M., Vitart V., Volker U., Vollenweider P., Volzke H., Wang Q., Wareham N.J., Weinberg C.R., Weir D.R., Wilcox A.N., van Dijk K.W., Willemsen G., Wilson J.F., Wolffenbuttel B.H.R., Wolk A., Wood A.R., Zhao W., Zygmunt M., Chen Z., Li L., Franke L., Burgess S., Deelen P., Pers T.H., Grondahl M.L., Andersen C.Y., Pujol A., Lopez-Contreras A.J., Daniel J.A., Stefansson K., Chang-Claude J., van der Schouw Y.T., Lunetta K.L., Chasman D.I., Easton D.F., Visser J.A., Ozanne S.E., Namekawa S.H., Solc P., Murabito J.M., Ong K.K., Hoffmann E.R., Murray A., Roig I., and Perry J.R.B.
- Abstract
Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
- Published
- 2021
5. Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample
- Author
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Fox, C.S., Larson, M.G., Hwang, S.-J., Leip, E.P., Rifai, N., Levy, D., Benjamin, E.J., Murabito, J.M., Meigs, J.B., and Vasan, R.S.
- Published
- 2006
- Full Text
- View/download PDF
6. Age-related DNA hydroxymethylation is enriched for gene expression and immune system processes in human peripheral blood
- Author
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Kiel, D.P., Huang, L., Li, R., Yang, Y., Jin, P., Murabito, J.M., Johnson, N.D., Grant, C., Whitsel, E.A., Wu, H., Conneely, K.N., Kim, H.R., Li, Y., and Baccarelli, A.A.
- Abstract
DNA methylation (DNAm) has a well-established association with age in many tissues, including peripheral blood mononuclear cells (PBMCs). Compared to DNAm, the closely related epigenetic modification known as DNA hydroxymethylation (DNAhm) was much more recently discovered in mammals. Preliminary investigations have observed a positive correlation between gene body DNAhm and cis-gene expression. While some of these studies have observed an association between age and global DNAhm, none have investigated region-specific age-related DNAhm in human blood samples. In this study, we investigated DNAhm and gene expression in PBMCs of 10 young and 10 old, healthy female volunteers. Thousands of regions were differentially hydroxymethylated in the old vs. young individuals in gene bodies, exonic regions, enhancers, and promoters. Consistent with previous work, we observed directional consistency between age-related differences in DNAhm and gene expression. Further, age-related DNAhm and genes with high levels of DNAhm were enriched for immune system processes which may support a role of age-related DNAhm in immunosenescence.
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- 2020
- Full Text
- View/download PDF
7. The complex genetics of gait speed: genome-wide meta-analysis approach (vol 9, pg 209, 2017)
- Author
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Ben-Avraham, D., Karasik, D., Verghese, J., Lunetta, K.L., Smith, J.A., Eicher, J.D., Vered, R., Deelen, J., Arnold, A.M., Buchman, A.S., Tanaka, T., Faul, J.D., Nethander, M., Fornage, M., Adams, H.H., Matteini, A.M., Callisaya, M.L., Smith, A.V., Yu, L., Jager, P.L. de, Evans, D.A., Gudnason, V., Hofman, A., Pattie, A., Corley, J., Launer, L.J., Knopman, D.S., Parimi, N., Turner, S.T., Bandinelli, S., Beekman, M., Gutman, D., Sharvit, L., Mooijaart, S.P., Liewald, D.C., Houwing-Duistermaat, J.J., Ohlsson, C., Moed, M., Verlinden, V.J., Mellstrom, D., Geest, J.N. van der, Karlsson, M., Hernandez, D., McWhirter, R., Liu, Y.M., Thomson, R., Tranah, G.J., Uitterlinden, A.G., Weir, D.R., Zhao, W., Starr, J.M., Johnson, A.D., Ikram, M.A., Bennett, D.A., Cummings, S.R., Deary, I.J., Harris, T.B., Kardia, S.L.R., Mosley, T.H., Srikanth, V.K., Windham, B.G., Newman, A.B., Walston, J.D., Davies, G., Evans, D.S., Slagboom, E.P., Ferrucci, L., Kiel, D.P., Murabito, J.M., and Atzmon, G.
- Published
- 2017
8. Corrigendum: Rare coding variants and X-linked loci associated with age at menarche
- Author
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Lunetta, K.L., Day, F.R., Sulem, P., Ruth, K.S., Tung, J.Y., Hinds, D.A., Esko, T., Elks, C.E., Altmaier, E., He, C., Huffman, J.E., Mihailov, E., Porcu, E., Robino, A., Rose, L.M., Schick, U.M., Stolk, L., Teumer, A., Thompson, D.J., Traglia, M., Wang, C.A., Yerges-Armstrong, L.M., Antoniou, A.C., Barbieri, C., Coviello, A.D., Cucca, F., Demerath, E.W., Dunning, A.M., Gandin, I., Grove, M.L., Gudbjartsson, D.F., Hocking, L.J., Hofman, A., Huang, J., Jackson, R.D., Karasik, D., Kriebel, J., Lange, E.M., Lange, L.A., Langenberg, C., Li, X., Luan, J., Mägi, R., Morrison, A.C., Padmanabhan, S., Pirie, A., Polasek, O., Porteous, D.J., Reiner, A.P., Rivadeneira, F., Rudan, I., Sala, C.F., Schlessinger, D., Scott, R.A., Stöckl, D., Visser, J.A., Völker, U., Vozzi, D., Wilson, J.G., Zygmunt, M., EPIC-Interact Consortium (), Generation Scotland Consortium (), Boerwinkle, E., Buring, J.E., Crisponi, L., Easton, D.F., Hayward, C., Hu, F.B., Liu, S., Metspalu, A., Pennell, C.E., Ridker, P.M., Strauch, K., Streeten, E.A., Toniolo, D., Uitterlinden, A.G., Ulivi, S., Völzke, H., Wareham, N.J., Wellons, M., Franceschini, N., Chasman, D.I., Thorsteinsdottir, U., Murray, A., Stefansson, K., Murabito, J.M., Ong, K.K., and Perry, J.R.
- Subjects
Adult ,Adolescent ,Genotype ,Mutation, Missense ,Immunoglobulins ,Cell Cycle Proteins ,Penetrance ,AMP-Activated Protein Kinases ,Autoantigens ,White People ,Young Adult ,Gene Frequency ,Genes, X-Linked ,Humans ,Aged ,Menarche ,Chromosomes, Human, X ,Hypogonadism ,Fatty Acids ,Age Factors ,Genetic Variation ,Membrane Proteins ,Proteins ,RNA-Binding Proteins ,Receptors, Neurokinin-3 ,Middle Aged ,Corrigenda ,Amides ,Phenotype ,Codon, Nonsense ,Female ,RNA Interference ,Laminin ,Energy Metabolism ,Signal Transduction - Abstract
More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
- Published
- 2015
9. New genetic loci link adipose and insulin biology to body fat distribution.
- Author
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ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., Carlson, OD., Egan, JM., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, ML., Loo, BM., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, HE., Deloukas, P., Katsareli, E., Couper, DJ., Duncan, BB., Kloppenburg, M., Adair, LS., Borja, JB., Wilson, JG., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, TM., Allison, MA., Redline, S., Buxbaum, SG., Mohlke, KL., Meulenbelt, I., Ballantyne, CM., Dedoussis, GV., Hu, FB., Liu, Y., Paulweber, B., Spector, TD., Slagboom, P., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, JC., Salomaa, V., Eriksson, JG., Frayling, TM., Hicks, AA., Lehtimäki, T., Smith, GD., Siscovick, DS., Kronenberg, F., van Duijn, C., Loos, RJ., Waterworth, DM., Meigs, JB., Dupuis, J., Richards, JB., Willenborg, C., Farrall, M., Assimes, TL., Thompson, JR., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, BA., Stirrups, K., König, IR., Cazier, JB., Johansson£££Åsa£££ Å., Hall, AS., Lee, JY., Willer, CJ., Chambers, JC., Esko£££Tõnu£££ T., Folkersen, L., Goel, A., Grundberg, E., Havulinna, AS., Ho, WK., Hopewell, JC., Eriksson, N., Kleber, ME., Lundmark, P., Lyytikäinen, LP., Rafelt, S., Shungin, D., Strawbridge, RJ., Thorleifsson, G., Tikkanen, E., Van Zuydam, N., Voight, BF., Waite, LL., Zhang, W., Ziegler, A., Absher, D., Altshuler, D., Balmforth, AJ., Barroso£££Inês£££ I., Braund, PS., Burgdorf, C., Claudi-Boehm, S., Cox, D., Dimitriou, M., Do, R., Doney, AS., El Mokhtari, N., Eriksson, P., Fischer, K., Fontanillas, P., Franco-Cereceda, A., Gigante, B., Groop, L., Gustafsson, S., Hager, J., Hallmans, G., Han, BG., Hunt, SE., Kang, HM., Illig, T., Kessler, T., Knowles, JW., Kolovou, G., Kuusisto, J., Langford, C., Leander, K., Lokki, ML., Lundmark, A., McCarthy, MI., Meisinger, C., Melander, O., Mihailov, E., Maouche, S., Morris, AD., Müller-Nurasyid, M., Nikus, K., Peden, JF., Rayner, NW., Rasheed, A., Rosinger, S., Rubin, D., Rumpf, MP., Schäfer, A., Sivananthan, M., Song, C., Stewart, AF., Tan, 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Zondervan, KT., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., Hillege, HL., van der Klauw MM., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Stolk, RP., Lagou, V., Welch, RP., Wheeler, E., Rehnberg, E., Yengo£££Loïc£££ L., Lecoeur, C., Johnson, PC., Mahajan, A., Verweij, N., Hottenga, JJ., Sennblad, B., Salo, P., Timpson, NJ., Hui, J., Bielak, LF., Zhao, W., Horikoshi, M., Navarro, P., Esko, T., Fall, T., Chen, H., Robertson, N., Rybin, D., Chines, PS., Song, K., An, P., Marullo, L., Jansen, H., Oldehinkel, AJ., North, KE., Forouhi, NG., Edkins, S., Varga, TV., Oksa, H., Antonella, M., Kong, A., Herder, C., Antti, J., Miljkovic, I., Atalay, M., Kiess, W., James, AL., Smit, JH., Campbell, S., Fowkes, GR., Basart, HV., Rathmann, W., Maerz, W., Province, MA., Watanabe, RM., de Geus EJ., Penninx, BW., Oostra, B., Toenjes, A., Peyser, PA., Körner, A., Keinanen-Kiukaanniemi, SM., Saaristo, TE., Boomsma, D., Cucca, F., Balkau, B., Froguel, P., Jarvelin, MR., Bouatia-Naji, N., Ahmadi, KR., Ainali, C., Barrett, A., Bataille, V., Bell, JT., Buil, A., Dermitzakis, ET., Dimas, AS., Durbin, R., Glass, D., Hassanali, N., Hedman£££Åsa K£££ ÅK., Ingle, C., Keildson, S., Knowles, D., Krestyaninova, M., Lowe, CE., Meduri, E., di Meglio, P., Min, JL., Montgomery, SB., Nestle, FO., Nica, AC., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, SY., Small, KS., Surdulescu, G., Travers, ME., Tsaprouni, L., Tsoka, S., Wilk, A., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., Heiss, G., Taylor, K., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Crawford, D., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Ritchie, M., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Peters, U., Anderson, G., Carlson, C., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Winkler, T.W., Croteau-Chonka, D.C., Locke, A.E., Strawbridge, R.J., Pers, T.H., Justice, A.E., Workalemahu, T., Wu, J.M., Buchkovich, M.L., Heard-Costa, N.L., Roman, T.S., Drong, A.W., Day, F.R., Luan, J., Randall, J.C., Scherag, A., Wood, A.R., Fehrmann, R., Karjalainen, J., Kahali, B., Liu, C.T., Schmidt, E.M., Anderson, D., Bragg-Gresham, J.L., Ehret, G.B., Feitosa, M.F., Jackson, A.U., Kleber, M.E., Mateo Leach, I., Medina-Gomez, C., Palmer, C.D., Pasko, D., Pechlivanis, S., Peters, M.J., Ju Sung, Y., Van Vliet-Ostaptchouk, J.V., Yengo, L., Arscott, G.M., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bonnet, F., Böttcher, Y., Carba, D.B., Caspersen, I.H., Daw, E.W., Deelen, J., Delgado, G., Doney, A.S., Eklund, N., Erdos, M.R., Eury, E., Friedrich, N., Garcia, M.E., Giedraitis, V., Go, A.S., Golay, A., Grammer, T.B., Gräßler, J., Grewal, J., Groves, C.J., Hartman, C.A., Hassinen, M., Herzig, K.H., Helmer, Q., Hillege, H.L., Holmen, O., Hunt, S.C., Ittermann, T., James, A.L., Johansson, I., Juliusdottir, T., Kalafati, I.P., Kinnunen, L., Kooner, I.K., Lee, N.R., Lichtner, P., Lobbens, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Mills, R., Monda, K.L., Mooijaart, S.P., Mühleisen, T.W., Mulas, A., Nalls, M.A., Glorioso, N., Nolte, I.M., Rayner, N.W., Renstrom, F., Ried, J.S., Robertson, N.R., Rose, L.M., Scholtens, S., Seufferlein, T., Sitlani, C.M., Vernon Smith, A., Stringham, H.M., Sundström, J., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tayo, B.O., Tomaschitz, A., Troffa, C., van Oort, F.V., Vonk, J.M., Waite, L.L., Wennauer, R., Wojczynski, M.K., Zhang, Q., Hua Zhao, J., Brennan, E.P., Choi, M., Gharavi, A.G., Hedman, Å.K., Hivert, M.F., Huang, J., Karpe, F., Kiryluk, K., Liang, L., Lifton, R.P., Ma, B., McKnight, A.J., McPherson, R., Min, J.L., Moffatt, M.F., Montgomery, G.W., Murabito, J.M., Nicholson, G., Nyholt, D.R., Olsson, C., Perry, J.R., Reinmaa, E., Salem, R.M., Schadt, E.E., Scott, R.A., Vallejo, E.E., Westra, H.J., Zondervan, K.T., Bakker, S.J., Beilby, J., Bergman, R.N., Blangero, J., Brown, M.J., Chines, P.S., Collins, F.S., Crawford, D.C., de Geus, E.J., Erbel, R., Eriksson, J.G., Ferrannini, E., Forouhi, N.G., Franco, O.H., Gansevoort, R.T., Haiman, C.A., Harris, T.B., Hattersley, A.T., Heliövaara, M., Hicks, A.A., Hingorani, A.D., Hoffmann, W., Humphries, S.E., Jarvelin, M.R., Johansen, B., Jousilahti, P., Jula, A.M., Keinanen-Kiukaanniemi, S.M., Kooner, J.S., Kraja, A.T., Lakka, T.A., Le Marchand, L., Lyssenko, V., Männistö, S., Marette, A., Matise, T.C., McKenzie, C.A., Musk, A.W., Möhlenkamp, S., Morris, A.D., Oldehinkel, A.J., Ong, K.K., Palmer, L.J., Penninx, B.W., Pramstaller, P.P., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Ridker, P.M., Ritchie, M.D., Samani, N.J., Sarzynski, M.A., Schwarz, P.E., Shuldiner, A.R., Staessen, J.A., Steinthorsdottir, V., Stolk, R.P., Strauch, K., Tremblay, A., Vohl, M.C., Wilson, J.F., Witteman, J.C., Adair, L.S., Boehm, B.O., Bornstein, S.R., Bouchard, C., Cauchi, S., Caulfield, M.J., Chambers, J.C., Chasman, D.I., Cooper, R.S., Grabe, H.J., Jöckel, K.H., Munroe, P.B., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Pérusse, L., Saaristo, T.E., Slagboom, P.E., Spector, T.D., Uitterlinden, A.G., Veronesi, G., Walker, M., Wareham, N.J., Wichmann, H.E., Abecasis, G.R., Assimes, T.L., Berndt, S.I., Borecki, I.B., Frayling, T.M., Groop, L.C., Hunter, D.J., Kaplan, R.C., O'Connell, J.R., Strachan, D.P., van Duijn, C.M., Willer, C.J., Visscher, P.M., Yang, J., Hirschhorn, J.N., Zillikens, M.C., McCarthy, M.I., Speliotes, E.K., North, K.E., Fox, C.S., Franks, P.W., Heid, I.M., Loos, R.J., Cupples, L.A., Morris, A.P., Lindgren, C.M., and Mohlke, K.L.
- Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
- Published
- 2015
10. Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events
- Author
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Fowkes, F.G.R., Murray, G.D., Butcher, I., Folsom, A.R., Hirsch, A.T., Couper, D.J., deBacker, G., Kornitzer, M., Newman, A.B., Sutton-Tyrrell, K.C., Cushman, M., Lee, A.J., Price, J.F., D'Agostino, R.B., Murabito, J.M., Norman, P.E., Masaki, K.H., Bouter, L.M., Heine, R.J., Stehouwer, C.D.A., McDermott, M.M., Stoffers, H.E.J.H., Knottnerus, J.A., Ogren, M., Hedblad, B., Koenig, W., Meisinger, C., Cauley, J.A., Franco, O.H., Hunink, M.G.M., Hofman, A., Witteman, J.C., Criqui, M.H., Langer, R.D., Hiatt, W.R., Hamman, R.F., Fowkes, F.G.R., Murray, G.D., Butcher, I., Folsom, A.R., Hirsch, A.T., Couper, D.J., deBacker, G., Kornitzer, M., Newman, A.B., Sutton-Tyrrell, K.C., Cushman, M., Lee, A.J., Price, J.F., D'Agostino, R.B., Murabito, J.M., Norman, P.E., Masaki, K.H., Bouter, L.M., Heine, R.J., Stehouwer, C.D.A., McDermott, M.M., Stoffers, H.E.J.H., Knottnerus, J.A., Ogren, M., Hedblad, B., Koenig, W., Meisinger, C., Cauley, J.A., Franco, O.H., Hunink, M.G.M., Hofman, A., Witteman, J.C., Criqui, M.H., Langer, R.D., Hiatt, W.R., and Hamman, R.F.
- Abstract
Background: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. Design: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. Methods: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS+ABI, were fitted for the primary outcome of major coronary events. © 2013 The European Society of Cardiology.
- Published
- 2014
- Full Text
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11. A genome-wide association study of early menopause and the combined impact of identified variants.
- Author
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ReproGen Consortium, Perry, J.R., Corre, T., Esko, T., Chasman, D.I., Fischer, K., Franceschini, N., He, C., Kutalik, Z., Mangino, M., Rose, L.M., Vernon Smith, A., Stolk, L., Sulem, P., Weedon, M.N., Zhuang, W.V., Arnold, A., Ashworth, A., Bergmann, S., Buring, J.E., Burri, A., Chen, C., Cornelis, M.C., Couper, D.J., Goodarzi, M.O., Gudnason, V., Harris, T., Hofman, A., Jones, M., Kraft, P., Launer, L., Laven, J.S., Li, G., McKnight, B., Masciullo, C., Milani, L., Orr, N., Psaty, B.M., Ridker, P.M., Rivadeneira, F., Sala, C., Salumets, A., Schoemaker, M., Traglia, M., Waeber, G., Chanock, S.J., Demerath, E.W., Garcia, M., Hankinson, S.E., Hu, F.B., Hunter, D.J., Lunetta, K.L., Metspalu, A., Montgomery, G.W., Murabito, J.M., Newman, A.B., Ong, K.K., Spector, T.D., Stefansson, K., Swerdlow, A.J., Thorsteinsdottir, U., Van Dam, R.M., Uitterlinden, A.G., Visser, J.A., Vollenweider, P., Toniolo, D., Murray, A., ReproGen Consortium, Perry, J.R., Corre, T., Esko, T., Chasman, D.I., Fischer, K., Franceschini, N., He, C., Kutalik, Z., Mangino, M., Rose, L.M., Vernon Smith, A., Stolk, L., Sulem, P., Weedon, M.N., Zhuang, W.V., Arnold, A., Ashworth, A., Bergmann, S., Buring, J.E., Burri, A., Chen, C., Cornelis, M.C., Couper, D.J., Goodarzi, M.O., Gudnason, V., Harris, T., Hofman, A., Jones, M., Kraft, P., Launer, L., Laven, J.S., Li, G., McKnight, B., Masciullo, C., Milani, L., Orr, N., Psaty, B.M., Ridker, P.M., Rivadeneira, F., Sala, C., Salumets, A., Schoemaker, M., Traglia, M., Waeber, G., Chanock, S.J., Demerath, E.W., Garcia, M., Hankinson, S.E., Hu, F.B., Hunter, D.J., Lunetta, K.L., Metspalu, A., Montgomery, G.W., Murabito, J.M., Newman, A.B., Ong, K.K., Spector, T.D., Stefansson, K., Swerdlow, A.J., Thorsteinsdottir, U., Van Dam, R.M., Uitterlinden, A.G., Visser, J.A., Vollenweider, P., Toniolo, D., and Murray, A.
- Abstract
Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.
- Published
- 2013
12. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies
- Author
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Murabito, J.M., White, C.C., Kavousi, M., Sun, Y.V., Feitosa, M.F., Nambi, V., Lamina, C., Schillert, A., Coassin, S., Bis, J.C., Broer, L., Crawford, D.C., Franceschini, N., Frikke-Schmidt, R., Haun, M., Holewijn, S., Huffman, J.E., Hwang, S.J., Kiechl, S., Kollerits, B., Montasser, M.E., Nolte, I.M., Rudock, M.E., Senft, A., Teumer, A., van der Harst, P., Vitart, V., Waite, L.L., Wood, A.R., Wassel, C.L., Absher, D.M., Allison, M.A., Amin, N., Arnold, A., Asselbergs, F.W., Aulchenko, Y., Bandinelli, S., Barbalic, M., Boban, M., Brown-Gentry, K., Couper, D.J., Criqui, M.H., Dehghan, A., den Heijer, M., Dieplinger, B., Ding, J.Z., Dorr, M., Espinola-Klein, C., Felix, S.B., Ferrucci, L., Folsom, A.R., Fraedrich, G., Gibson, Q., Goodloe, R., Gunjaca, G., Haltmayer, M., Heiss, G., Hofman, A., Kieback, A., Kiemeney, L.A., Kolcic, I., Kullo, I.J., Kritchevsky, S.B., Lackner, K.J., Li, X.H., Lieb, W.G., Lohman, K., Meisinger, C., Melzer, D., Mohler, E.R., Mudnic, I., Mueller, T., Navis, G., Oberhollenzer, F., Olin, J.W., O'Connell, J., O'Donnell, C.J., Palmas, W., Penninx, B.W.J.H., Petersmann, A., Polasek, O., Psaty, B.M., Rantner, B., Rice, K., Rivadeneira, F., Rotter, J.I., Seldenrijk, A., Stadler, M., Summerer, M., Tanaka, T., Tybjaerg-Hansen, A., Uitterlinden, A. G., van Gilst, W.H., Vermeulen, S.H., Wild, S.H., Wild, P.S., Willeit, J., Zeller, T., Zemunik, T., Murabito, J.M., White, C.C., Kavousi, M., Sun, Y.V., Feitosa, M.F., Nambi, V., Lamina, C., Schillert, A., Coassin, S., Bis, J.C., Broer, L., Crawford, D.C., Franceschini, N., Frikke-Schmidt, R., Haun, M., Holewijn, S., Huffman, J.E., Hwang, S.J., Kiechl, S., Kollerits, B., Montasser, M.E., Nolte, I.M., Rudock, M.E., Senft, A., Teumer, A., van der Harst, P., Vitart, V., Waite, L.L., Wood, A.R., Wassel, C.L., Absher, D.M., Allison, M.A., Amin, N., Arnold, A., Asselbergs, F.W., Aulchenko, Y., Bandinelli, S., Barbalic, M., Boban, M., Brown-Gentry, K., Couper, D.J., Criqui, M.H., Dehghan, A., den Heijer, M., Dieplinger, B., Ding, J.Z., Dorr, M., Espinola-Klein, C., Felix, S.B., Ferrucci, L., Folsom, A.R., Fraedrich, G., Gibson, Q., Goodloe, R., Gunjaca, G., Haltmayer, M., Heiss, G., Hofman, A., Kieback, A., Kiemeney, L.A., Kolcic, I., Kullo, I.J., Kritchevsky, S.B., Lackner, K.J., Li, X.H., Lieb, W.G., Lohman, K., Meisinger, C., Melzer, D., Mohler, E.R., Mudnic, I., Mueller, T., Navis, G., Oberhollenzer, F., Olin, J.W., O'Connell, J., O'Donnell, C.J., Palmas, W., Penninx, B.W.J.H., Petersmann, A., Polasek, O., Psaty, B.M., Rantner, B., Rice, K., Rivadeneira, F., Rotter, J.I., Seldenrijk, A., Stadler, M., Summerer, M., Tanaka, T., Tybjaerg-Hansen, A., Uitterlinden, A. G., van Gilst, W.H., Vermeulen, S.H., Wild, S.H., Wild, P.S., Willeit, J., Zeller, T., and Zemunik, T.
- Abstract
Background-Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Methods and Results-Continuous ABI and PAD (ABI <0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the <2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed effects inverse variance weighted meta-analyses. There were a total of 41 692 participants of European ancestry (<60% women, mean ABI 1.02 to 1.19), including 3409 participants with PAD and with genome-wide association study data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β-0.006, P=2.46×10-8). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16 717). The association for rs10757269 strengthened in the combined discovery and replication analysis (P=2.65×10-9). No other SNP associations for ABI or PAD achieved genome-wide significance. However, 2 previously reported candidate genes for PAD and 1 SNP associated with coronary artery disease were associated with ABI: DAB21P (rs13290547, P=3.6×10-5), CYBA (rs3794624, P=6.3×10-5), and rs1122608 (LDLR, P=0.0026). Conclusions-Genome-wide association studies in more than 40 000 individuals identified 1 genome wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for coronary artery disease are associated with ABI. © 2012 American Heart Association, Inc.
- Published
- 2012
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13. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms
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Zhai, G., Teumer, A., Stolk, L., Perry, J.R., Vandenput, L., Coviello, A.D., Koster, A., Bell, J.T., Bhasin, S., Eriksson, J., Eriksson, A., Ernst, F., Ferrucci, L., Frayling, T.M., Glass, D., Grundberg, E., Haring, R., Hedman, A.K., Hofman, A., Kiel, D.P., Kroemer, H.K., Liu, Y., Lunetta, K.L., Maggio, M., Lorentzon, M., Mangino, M., Melzer, D., Miljkovic, I., Nica, A., Penninx, B.W.J.H., Vasan, R.S., Rivadeneira, F., Small, K.S., Soranzo, N., Uitterlinden, A. G., Voelzke, H., Wilson, S.G., Xi, L., Zhuang, W.V., Harris, T.B., Murabito, J.M., Ohlsson, C., Murray, A., de Jong, F.H., Spector, T.D., Wallaschofski, H., Zhai, G., Teumer, A., Stolk, L., Perry, J.R., Vandenput, L., Coviello, A.D., Koster, A., Bell, J.T., Bhasin, S., Eriksson, J., Eriksson, A., Ernst, F., Ferrucci, L., Frayling, T.M., Glass, D., Grundberg, E., Haring, R., Hedman, A.K., Hofman, A., Kiel, D.P., Kroemer, H.K., Liu, Y., Lunetta, K.L., Maggio, M., Lorentzon, M., Mangino, M., Melzer, D., Miljkovic, I., Nica, A., Penninx, B.W.J.H., Vasan, R.S., Rivadeneira, F., Small, K.S., Soranzo, N., Uitterlinden, A. G., Voelzke, H., Wilson, S.G., Xi, L., Zhuang, W.V., Harris, T.B., Murabito, J.M., Ohlsson, C., Murray, A., de Jong, F.H., Spector, T.D., and Wallaschofski, H.
- Abstract
Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10
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- 2011
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14. Genetic determinants of serum testosterone concentrations in men
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Ohlsson, C., Wallaschofski, H., Lunetta, K.L., Stolk, L., Perry, J.R.B., Koster, A., Petersen, A.K., Eriksson, J., Lehtimaki, T., Huhtaniemi, I.T., Hammond, G.L., Maggio, M., Coviello, A.D., Ferrucci, L., Heier, M., Hofman, A., Holliday, K.L., Jansson, J.O., Kahonen, M., Karasik, D., Karlsson, M.K., Kiel, D.P., Liu, Y.M., Ljunggren, O., Lorentzon, M., Lyytikainen, L.P., Meitinger, T., Mellstrom, D., Melzer, D., Miljkovic, I., Nauck, M., Nilsson, M., Penninx, B.W.J.H., Pye, S.R., Vasan, R.S., Reincke, M., Rivadeneira, F., Tajar, A., Teumer, A., Uitterlinden, A. G., Ulloor, J., Viikari, J., Volker, U., Volzke, H., Wichmann, H. E., Wu, T.S., Zhuang, W.V., Ziv, E., Wu, F.C.W., Raitakari, O., Eriksson, A., Bidlingmaier, M., Harris, T.B., Murray, A., de Jong, F.H., Murabito, J.M., Bhasin, S., Vandenput, L., Haring, R., Ohlsson, C., Wallaschofski, H., Lunetta, K.L., Stolk, L., Perry, J.R.B., Koster, A., Petersen, A.K., Eriksson, J., Lehtimaki, T., Huhtaniemi, I.T., Hammond, G.L., Maggio, M., Coviello, A.D., Ferrucci, L., Heier, M., Hofman, A., Holliday, K.L., Jansson, J.O., Kahonen, M., Karasik, D., Karlsson, M.K., Kiel, D.P., Liu, Y.M., Ljunggren, O., Lorentzon, M., Lyytikainen, L.P., Meitinger, T., Mellstrom, D., Melzer, D., Miljkovic, I., Nauck, M., Nilsson, M., Penninx, B.W.J.H., Pye, S.R., Vasan, R.S., Reincke, M., Rivadeneira, F., Tajar, A., Teumer, A., Uitterlinden, A. G., Ulloor, J., Viikari, J., Volker, U., Volzke, H., Wichmann, H. E., Wu, T.S., Zhuang, W.V., Ziv, E., Wu, F.C.W., Raitakari, O., Eriksson, A., Bidlingmaier, M., Harris, T.B., Murray, A., de Jong, F.H., Murabito, J.M., Bhasin, S., Vandenput, L., and Haring, R.
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- 2011
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15. Ankle brachial index combined with Framingham risk score to predict cardiovascular events and mortality - A meta-analysis
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Fowkes, F.G.R., Murray, G.D., Butcher, I., Heald, C.L., Lee, R.J., Chambless, L.E., Folsom, A.R., Hirsch, A.T., Dramaix, M., deBacker, G., Wautrecht, J.C., Kornitzer, M., Newman, A.B., Cushman, M., Sutton-Tyrrell, K., Lee, A.J., Price, J.F., D'Agostino, R.B., Murabito, J.M., Norman, P.E., Jamrozik, K., Curb, J.D., Masaki, K.H., Rodriquez, B.L., Dekker, J.M., Bouter, L.M., Heine, R.J., Nijpels, G., Stehouwer, C.D.A., Ferrucci, L., Stoffers, H.E., Hooi, J.D., Knottnerus, J.A., Ogren, M., Hedblad, B., Witteman, J.C., Breteler, M.M.B., Hunink, M.G.M., Hofman, A., Criqui, M.H., Langer, R.D., Fronek, A., Hiatt, W.R., Hamman, R., Resnick, H.E., Guralnik, J., McDermott, M.M., Fowkes, F.G.R., Murray, G.D., Butcher, I., Heald, C.L., Lee, R.J., Chambless, L.E., Folsom, A.R., Hirsch, A.T., Dramaix, M., deBacker, G., Wautrecht, J.C., Kornitzer, M., Newman, A.B., Cushman, M., Sutton-Tyrrell, K., Lee, A.J., Price, J.F., D'Agostino, R.B., Murabito, J.M., Norman, P.E., Jamrozik, K., Curb, J.D., Masaki, K.H., Rodriquez, B.L., Dekker, J.M., Bouter, L.M., Heine, R.J., Nijpels, G., Stehouwer, C.D.A., Ferrucci, L., Stoffers, H.E., Hooi, J.D., Knottnerus, J.A., Ogren, M., Hedblad, B., Witteman, J.C., Breteler, M.M.B., Hunink, M.G.M., Hofman, A., Criqui, M.H., Langer, R.D., Fronek, A., Hiatt, W.R., Hamman, R., Resnick, H.E., Guralnik, J., and McDermott, M.M.
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- 2008
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16. Smoking, Alcohol Consumption, and Raynaud’s Phenomenon in Middle-Age
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Suter, L.G., primary, Murabito, J.M., additional, and Felson, D.T., additional
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- 2007
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17. Unexplained gradual-onset Q wave patterns
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Murabito, J.M., Larson, M.G., Lin, S.T., Evans, J.C., and Levy, D.
- Abstract
Original cohort members of the Framingham Study were studied to determine prognosis associated with unexplained (gradual-onset) Q wave patterns detected on routine electrocardiograms (ECGs). Biennial ECGs were obtained on subjects beginning in 1948. The index ECG was read independently and then serially in relation to all previous tracings for evidence of myocardial infarction. Proportional hazards modeling was used to assess the risk for outcomes in those with unexplained (gradual-onset) Q wave patterns compared with subjects with unrecognized myocardial infarcts (abrupt-onset Q waves) and compared with referent subjects. Unexplained Q wave patterns developed in 53 men and 39 women. Subjects with unexplained Q wave patterns had less than 40% of the risk for myocardial infarction or coronary death as compared with those with unrecognized myocardial infarction after adjusting for risk factors (hazard ratio, 0.38; 95% confidence interval, 0.19, 0.78; P = .008) and a trend toward a lower risk for overall mortality (adjusted hazard ratio, 0.73; 95% confidence interval, 0.46, 1.16; P = .18). Risks for myocardial infarction or coronary death and overall mortality were similar in subjects with unexplained Q wave patterns and referent subjects in the fully adjusted models. Detection of prominent Q waves on an ECG requires comparison with prior tracings to differentiate the unexplained Q wave pattern from the unrecognized infarct, conditions that have significantly different prognostic implications.
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- 1995
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