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 journalArticlepeer-review

16 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

Bibliographical note

Funding Information:
The PAGE consortium thanks the staff and participants of all PAGE studies for their important contributions. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The complete list of PAGE members can be found at http://www.pagestudy. org. Assistance with phenotype harmonization, SNP selection and annotation, data cleaning, data management, integration and dissemination, and general study coordination was provided by the PAGE Coordinating Center (U01HG004801-01 and its NHGRI ARRA supplement). The National Institutes of Mental Health also contributes to the support for the Coordinating Center. See Detailed Acknowledgment in Supplementary Information for PAGE study-specific acknowledgements. The PAGE program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI), and U01HG004801 (Coordinating Center), and their respective NHGRI ARRA supplements.

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