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  • Talmud, Philippa J. (author)

Gene-centric Association Signals for Lipids and Apolipoproteins Identified via the HumanCVD BeadChip

  • Article/chapterEnglish2009

Publisher, publication year, extent ...

  • Elsevier BV,2009

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:3efaeff4-5eb5-4d40-8246-75f3495eb383
  • https://lup.lub.lu.se/record/1518531URI
  • https://doi.org/10.1016/j.ajhg.2009.10.014DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Blood lipids are important cardiovascular disease (CVD) risk factors with both genetic and environmental determinants. The Whitehall II study (n = 5592) was genotyped with the gene-centric HumanCVD BeadChip (Illumina). We identified 195 SNPs in 16 genes/regions associated with 3 major lipid fractions and 2 apolipoprotein components at p < 10(-5), with the associations being broadly concordant with prior genome-wide analysis. SNPs associated with LDL cholesterol and apolipoprotein B were located in LDLR, PCSK9, APOB, CELSR2, HWGCR, CETP, the TOMM40-APOE-C1-C2-C4 cluster, and the APOA5-A4-C3-A1 cluster; SNPs associated with HDL cholesterol and apolipoprotein AI were in CETP, LPL, LIPC, APOA5-A4-C3-A1, and ABCA1; and SNPs associated with triglycerides in GCKR, BAZIB, MLXIPL, LPL, and APOA5-A4-C3-A1. For 48 SNPs in previously unreported loci that were significant at p < 10(-4) in Whitehall II, in silico analysis including the British Women's Heart and Health Study, BRIGHT, ASCOT, and NORDIL studies (total n > 12,500) revealed previously unreported associations of SH2B3 (p < 2.2 x 10(-6)), BMPR2 (p < 2.3 x 10(-7)), BCL3/PVRL2 (flanking APOE; p < 4.4 x 10(-8)), and SMARCA4 (flanking LDLR; p < 2.5 x 10(-7)) with LDL cholesterol. Common alleles in these genes explained 6.1%-14.7% of the variance in the five lipid-related traits, and individuals at opposite tails of the additive allele score exhibited substantial differences in trait levels (e.g., > 1 mmol/L in LDL cholesterol [similar to 1 SD of the trait distribution]). These data suggest that multiple common alleles of small effect can make important contributions to individual differences in blood lipids potentially relevant to the assessment of CVD risk. These genes provide further insights into lipid metabolism and the likely effects of modifying the encoded targets therapeutically.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Drenos, Fotios (author)
  • Shah, Sonia (author)
  • Shah, Tina (author)
  • Palmen, Jutta (author)
  • Verzilli, Claudio (author)
  • Gaunt, Tom R. (author)
  • Pallas, Jacky (author)
  • Lovering, Ruth (author)
  • Li, Kawah (author)
  • Casas, Juan Pablo (author)
  • Sofat, Reecha (author)
  • Kumari, Meena (author)
  • Rodriguez, Santiago (author)
  • Johnson, Toby (author)
  • Newhouse, Stephen J. (author)
  • Dominiczak, Anna (author)
  • Samani, Nilesh J. (author)
  • Caulfield, Mark (author)
  • Sever, Peter (author)
  • Stanton, Alice (author)
  • Shields, Denis C. (author)
  • Padmanabhan, Sandosh (author)
  • Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
  • Hastie, Claire (author)
  • Delles, Christian (author)
  • Ebrahim, Shah (author)
  • Marmot, Michael G. (author)
  • Smith, George Davey (author)
  • Lawlor, Debbie A. (author)
  • Munroe, Patricia B. (author)
  • Day, Ian N. (author)
  • Kivimaki, Mika (author)
  • Whittaker, John (author)
  • Humphries, Steve E. (author)
  • Hingorani, Aroon D. (author)
  • Kardiovaskulär forskning - hypertoniForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:American Journal of Human Genetics: Elsevier BV85:5, s. 628-6420002-9297

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