Fine-Mapping of Lipid Regions in Global Populations Discovers Ethnic-Specific Signals and Refines Previously Identified Lipid Loci

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Citation

Zubair, Niha; Graff, Mariaelisa; Ambite, Jose Luis; Bush, William S.; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne Huey-Herng; Absher, Devin M.; & Assimes, Themistocles L., et al. (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. PMCID: PMC5721937

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.

URL

http://dx.doi.org/10.1093/hmg/ddw358

Reference Type

Journal Article

Year Published

2016

Journal Title

Human Molecular Genetics

Author(s)

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

PMCID

PMC5721937

ORCiD

Graff - 0000-0001-6380-1735