Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study

Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study. Hu, Y., Graff, M., Haessler, J., Buyske, S., Bien, S. A, Tao, R., Highland, H. M, Nishimura, K. K, Zubair, N., Lu, Y., Verbanck, M., Hilliard, A. T, Klarin, D., Damrauer, S. M, Ho, Y., VA Million Veteran Program, Wilson, P. W F, Chang, K., Tsao, P. S, Cho, K., O'Donnell, C. J, Assimes, T. L, Petty, L. E, Below, J. E, Dikilitas, O., Schaid, D. J, Kosel, M. L, Kullo, I. J, Rasmussen-Torvik, L. J, Jarvik, G. P, Feng, Q., Wei, W., Larson, E. B, Mentch, F. D, Almoguera, B., Sleiman, P. M, Raffield, L. M, Correa, A., Martin, L. W, Daviglus, M., Matise, T. C, Ambite, J. L., Carlson, C. S, Do, R., Loos, R. J F, Wilkens, L. R, Le Marchand, L., Haiman, C., Stram, D. O, Hindorff, L. A, North, K. E, Kooperberg, C., Cheng, I., & Peters, U. PLoS Genet, 16(3):e1008684, Mar, 2020.

Paper doi abstract bibtex 6 downloads

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.

@article{Hu:2020uj,
	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.},
	author = {Hu, Yao and Graff, Mariaelisa and Haessler, Jeffrey and Buyske, Steven and Bien, Stephanie A and Tao, Ran and Highland, Heather M and Nishimura, Katherine K and Zubair, Niha and Lu, Yingchang and Verbanck, Marie and Hilliard, Austin T and Klarin, Derek and Damrauer, Scott M and Ho, Yuk-Lam and {VA Million Veteran Program} and Wilson, Peter W F and Chang, Kyong-Mi and Tsao, Philip S and Cho, Kelly and O'Donnell, Christopher J and Assimes, Themistocles L and Petty, Lauren E and Below, Jennifer E and Dikilitas, Ozan and Schaid, Daniel J and Kosel, Matthew L and Kullo, Iftikhar J and Rasmussen-Torvik, Laura J and Jarvik, Gail P and Feng, Qiping and Wei, Wei-Qi and Larson, Eric B and Mentch, Frank D and Almoguera, Berta and Sleiman, Patrick M and Raffield, Laura M and Correa, Adolfo and Martin, Lisa W and Daviglus, Martha and Matise, Tara C and Ambite, Jose Luis and Carlson, Christopher S and Do, Ron and Loos, Ruth J F and Wilkens, Lynne R and Le Marchand, Loic and Haiman, Chris and Stram, Daniel O and Hindorff, Lucia A and North, Kari E and Kooperberg, Charles and Cheng, Iona and Peters, Ulrike},
	date-added = {2021-06-15 23:01:04 -0400},
	date-modified = {2021-06-15 23:01:04 -0400},
	doi = {10.1371/journal.pgen.1008684},
	journal = {PLoS Genet},
	journal-full = {PLoS genetics},
	mesh = {Continental Population Groups; Databases, Genetic; Female; Genome-Wide Association Study; Genotype; Humans; Lipids; Male; Metagenomics; Minority Groups; Multifactorial Inheritance; Phenotype; Polymorphism, Single Nucleotide; United States},
	month = {Mar},
	number = {3},
	pages = {e1008684},
	pmc = {PMC7145272},
	pmid = {32226016},
	url = {https://pubmed.ncbi.nlm.nih.gov/32226016/},
	pst = {epublish},
	title = {Minority-centric meta-analyses of blood lipid levels identify novel loci in the {Population Architecture using Genomics and Epidemiology} ({PAGE}) study},
	volume = {16},
	year = {2020},
	bdsk-url-1 = {https://doi.org/10.1371/journal.pgen.1008684}}

Downloads: 6