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Large scale replication analysis of loci associated with lipid concentrations in a Japanese population
  1. K Nakayama1,
  2. T Bayasgalan2,
  3. K Yamanaka1,
  4. M Kumada1,3,
  5. T Gotoh1,
  6. N Utsumi1,
  7. Y Yanagisawa1,
  8. M Okayama3,
  9. E Kajii3,
  10. S Ishibashi2,
  11. S Iwamoto1,
  12. The Jichi Community Genetics Team (JCOG)3
  1. 1
    Division of Human Genetics, Center of Community Medicine, Jichi Medical University, Shimotsuke-city, Japan
  2. 2
    Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, Shimotsuke-city, Japan
  3. 3
    Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Shimotsuke-city, Japan
  1. Dr S Iwamoto, Division of Human Genetics, Center for Community Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-city, Tochigi, 329-0498 Japan; siwamoto{at}jichi.ac.jp

Abstract

Background: Recent genome wide association studies discovered seven novel loci that influence plasma concentrations of triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in Europeans. To date, large scale replication studies using populations with known differences in genome-wide linkage disequilibrium (LD) pattern have not been undertaken.

Methods: To address this issue, we tested associations between single nucleotide polymorphisms (SNPs) within the seven novel loci and plasma lipid profiles in 21 010 Japanese individuals.

Results: Multiple linear regression analyses showed that the rs3812316 in MLXIPL was strongly associated with triglyceride concentrations (p∼3.0×10−11, 7.1 mg/dl decrease per minor C allele) and that rs599839 in CELSR2/PSRC1/SORT1 was strongly associated with LDL cholesterol concentrations (p∼3.1×10−11, 4.7 mg/dl decrease per minor G allele) in the Japanese population. SNPs near ANGPTL3, TRIB1 and GALNT2 showed evidence for associations with triglyceride concentrations (3.6×10−6<p<5.1×10−5). SNP near TRIB1 showed association with LDL cholesterol concentrations (p∼1.2×10−5). On the other hand, SNPs in NCAN/CILP2/PBX4 and MVK/MMAB were not associated with any plasma lipid profiles in the Japanese population. Ethnic differences in LD pattern would explain the lack of association between these two loci and plasma lipid concentrations in the Japanese population.

Conclusion: Associations between the novel loci and plasma lipid concentrations were generally conserved in the Japanese population, with the exception of NCAN/CILP2/PBX4 and MVK/MMAB.

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Footnotes

  • Additional tables and fig, and full list of the Jichi Community Genetics Team (JCOG), are published online only at http://jmg.bmj.com/content/vol46/issue6

  • Funding: This study was supported in part by Grand-in-Aid for the 21st Century COE Program at Jichi Medical University, Jichi Medical University Young Investigator Award and Grant-in-Aid for Young Scientists (B) 19770214.

  • Competing interests: None.

  • Patient consent: Obtained.

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