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) approximately 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 approximately10% of the va...

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Published in:PLoS genetics 2011-10, Vol.7 (10), p.e1002298
Main Authors: 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
Format: Article
Language:English
Subjects:
Adult
African Americans
African Americans - genetics
Aged
Aged, 80 and over
Biology
Body Height - genetics
Breast cancer
Chromosome Mapping
European Continental Ancestry Group - genetics
Female
Gene Frequency
Genetic aspects
Genetics
Genome-Wide Association Study
Genomes
Genotype
Grants
Humans
Male
Medical research
Middle Aged
Phenotype
Physiological aspects
Polymorphism, Single Nucleotide
Population genetics
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Summary:Adult height is a classic polygenic trait of high heritability (h(2) approximately 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 approximately10% 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
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1002298