Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry

Adult height is a classic polygenic trait of high heritability (h (2) ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discov...

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Detalles Bibliográficos
Autores principales: N'Diaye, Amidou, Chen, Gary K., Palmer, Cameron D., Ge, Bing, Tayo, Bamidele, Mathias, Rasika A., Ding, Jingzhong, Nalls, Michael A., Adeyemo, Adebowale, Adoue, Véronique, Ambrosone, Christine B., Atwood, Larry, Bandera, Elisa V., Becker, Lewis C., Berndt, Sonja I., Bernstein, Leslie, Blot, William J., Boerwinkle, Eric, Britton, Angela, Casey, Graham, Chanock, Stephen J., Demerath, Ellen, Deming, Sandra L., Diver, W. Ryan, Fox, Caroline, Harris, Tamara B., Hernandez, Dena G., Hu, Jennifer J., Ingles, Sue A., John, Esther M., Johnson, Craig, Keating, Brendan, Kittles, Rick A., Kolonel, Laurence N., Kritchevsky, Stephen B., Le Marchand, Loic, Lohman, Kurt, Liu, Jiankang, Millikan, Robert C., Murphy, Adam, Musani, Solomon, Neslund-Dudas, Christine, North, Kari E., Nyante, Sarah, Ogunniyi, Adesola, Ostrander, Elaine A., Papanicolaou, George, Patel, Sanjay, Pettaway, Curtis A., Press, Michael F., Redline, Susan, Rodriguez-Gil, Jorge L., Rotimi, Charles, Rybicki, Benjamin A., Salako, Babatunde, Schreiner, Pamela J., Signorello, Lisa B., Singleton, Andrew B., Stanford, Janet L., Stram, Alex H., Stram, Daniel O., Strom, Sara S., Suktitipat, Bhoom, Thun, Michael J., Witte, John S., Yanek, Lisa R., Ziegler, Regina G., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Evans, Michele K., Liu, Yongmei, Becker, Diane M., Cooper, Richard S., Pastinen, Tomi, Henderson, Brian E., Hirschhorn, Joel N., Lettre, Guillaume, Haiman, Christopher A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188544/
https://www.ncbi.nlm.nih.gov/pubmed/21998595
http://dx.doi.org/10.1371/journal.pgen.1002298
Descripción
Sumario:Adult height is a classic polygenic trait of high heritability (h (2) ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10(−12) and 2p14-rs4315565, P = 1.2×10(−8)). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10(−4) for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.

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