Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

Niha Zubair, Mariaelisa Graff, Jose Luis Ambite, William S. Bush, Gleb Kichaev, Yingchang Lu, Ani Manichaikul, Wayne H.H. Sheu, Devin Absher, Themistocles L. Assimes, Suzette J. Bielinski, Erwin P. Bottinger, Petra Buzkova, Lee Ming Chuang, Ren Hua Chung, Barbara Cochran, Logan Dumitrescu, Omri Gottesman, Jeffrey W. Haessler, Christopher HaimanGerardo Heiss, Chao A. Hsiung, Yi Jen Hung, Chii Min Hwu, Jyh Ming J. Juang, Loic Le Marchand, I. Te Lee, Wen Jane Lee, Li An Lin, Danyu Lin, Shih Yi Lin, Rachel H. Mackey, Lisa W. Martin, Bogdan Pasaniuc, Ulrike Peters, Irene Predazzi, Thomas Quertermous, Alex P. Reiner, Jennifer Robinson, Jerome I. Rotter, Kelli K. Ryckman, Pamela J. Schreiner, Eli Stahl, Ran Tao, Michael Y. Tsai, Lindsay L. Waite, Tzung Dau Wang, Steven Buyske, Yii Der Ida Chen, Iona Cheng, Dana C. Crawford, Ruth J.F. Loos, Stephen S. Rich, Myriam Fornage, Kari E. North, Charles Kooperberg, Cara L. Carty

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown.We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies.

Original languageEnglish (US)
Pages (from-to)5500-5512
Number of pages13
JournalHuman molecular genetics
Volume25
Issue number24
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Zubair, N., Graff, M., Ambite, J. L., Bush, W. S., Kichaev, G., Lu, Y., Manichaikul, A., Sheu, W. H. H., Absher, D., Assimes, T. L., Bielinski, S. J., Bottinger, E. P., Buzkova, P., Chuang, L. M., Chung, R. H., Cochran, B., Dumitrescu, L., Gottesman, O., Haessler, J. W., ... Carty, C. L. (2016). Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci. Human molecular genetics, 25(24), 5500-5512. https://doi.org/10.1093/hmg/ddw358