| Title: | Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study |
| Journal: | PLOS Genetics |
| Published: | 30 Mar 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32226016/ |
| DOI: | https://doi.org/10.1371/journal.pgen.1008684 |
| URL: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008684&type=printable |
Publication 9108
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Abstract
Lipid levels are important markers for the development of cardio-metabolic diseases. Although hundreds of associated loci have been identified through genetic association studies, the contribution of genetic factors to variation in lipids is not fully understood, particularly in U.S. minority groups. We performed genome-wide association analyses for four lipid traits in over 45,000 ancestrally diverse participants from the Population Architecture using Genomics and Epidemiology (PAGE) Study, followed by a meta-analysis with several European ancestry studies. We identified nine novel lipid loci, five of which showed evidence of replication in independent studies. Furthermore, we discovered one novel gene in a PrediXcan analysis, minority-specific independent signals at eight previously reported loci, and potential functional variants at two known loci through fine-mapping. Systematic examination of known lipid loci revealed smaller effect estimates in African American and Hispanic ancestry populations than those in Europeans, and better performance of polygenic risk scores based on minority-specific effect estimates. Our findings provide new insight into the genetic architecture of lipid traits and highlight the importance of conducting genetic studies in diverse populations in the era of precision medicine.</p>
53 Authors
- Yao Hu
- Mariaelisa Graff
- Jeffrey Haessler
- Steven Buyske
- Stephanie A. Bien
- Ran Tao
- Heather M. Highland
- Katherine K. Nishimura
- Niha Zubair
- Yingchang Lu
- Marie Verbanck
- Austin T. Hilliard
- Derek Klarin
- Scott M. Damrauer
- Yuk-Lam Ho
- Peter W. F. Wilson
- Kyong-Mi Chang
- Philip S. Tsao
- Kelly Cho
- Christopher J. O'Donnell
- Themistocles L. Assimes
- Lauren E. Petty
- Jennifer E. Below
- Ozan Dikilitas
- Daniel J. Schaid
- Matthew L. Kosel
- Iftikhar J. Kullo
- Laura J. Rasmussen-Torvik
- Gail P. Jarvik
- Qiping Feng
- Wei-Qi Wei
- Eric B. Larson
- Frank D. Mentch
- Berta Almoguera
- Patrick M. Sleiman
- Laura M. Raffield
- Adolfo Correa
- Lisa W. Martin
- Martha Daviglus
- Tara C. Matise
- Jose Luis Ambite
- Christopher S. Carlson
- Ron Do
- Ruth J. F. Loos
- Lynne R. Wilkens
- Loic Le Marchand
- Chris Haiman
- Daniel O. Stram
- Lucia A. Hindorff
- Kari E. North
- Charles Kooperberg
- Iona Cheng
- Ulrike Peters
1 Application
| Application ID | Title |
|---|---|
| 42680 | Evaluating genome-wide association and genetic interaction in complex traits |
Enabling scientific discoveries that improve human health