Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry
Amidou N'Diaye,
Gary K Chen,
Cameron D Palmer,
Bing Ge,
Bamidele Tayo,
Rasika A Mathias,
Jingzhong Ding,
Michael A Nalls,
Adebowale Adeyemo,
Véronique Adoue,
Christine B Ambrosone,
Larry Atwood,
Elisa V Bandera,
Lewis C Becker,
Sonja I Berndt,
Leslie Bernstein,
William J Blot,
Eric Boerwinkle,
Angela Britton,
Graham Casey,
Stephen J Chanock,
Ellen Demerath,
Sandra L Deming,
W Ryan Diver,
Caroline Fox,
Tamara B Harris,
Dena G Hernandez,
Jennifer J Hu,
Sue A Ingles,
Esther M John,
Craig Johnson,
Brendan Keating,
Rick A Kittles,
Laurence N Kolonel,
Stephen B Kritchevsky,
Loic Le Marchand,
Kurt Lohman,
Jiankang Liu,
Robert C Millikan,
Adam Murphy,
Solomon Musani,
Christine Neslund-Dudas,
Kari E North,
Sarah Nyante,
Adesola Ogunniyi,
Elaine A Ostrander,
George Papanicolaou,
Sanjay Patel,
Curtis A Pettaway,
Michael F Press,
Susan Redline,
Jorge L Rodriguez-Gil,
Charles Rotimi,
Benjamin A Rybicki,
Babatunde Salako,
Pamela J Schreiner,
Lisa B Signorello,
Andrew B Singleton,
Janet L Stanford,
Alex H Stram,
Daniel O Stram,
Sara S Strom,
Bhoom Suktitipat,
Michael J Thun,
John S Witte,
Lisa R Yanek,
Regina G Ziegler,
Wei Zheng,
Xiaofeng Zhu,
Joseph M Zmuda,
Alan B Zonderman,
Michele K Evans,
Yongmei Liu,
Diane M Becker,
Richard S Cooper,
Tomi Pastinen,
Brian E Henderson,
Joel N Hirschhorn,
Guillaume Lettre and
Christopher A Haiman
PLOS Genetics, 2011, vol. 7, issue 10, 1-11
Abstract:
Adult height is a classic polygenic trait of high heritability (h2 ∼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 180 single nucleotide polymorphisms (SNPs) associated with height. In the current study, we continued to use height as a model polygenic trait and explored the genetic influence in populations of African ancestry through a meta-analysis of GWA height results from 20,809 individuals of African descent. We identified two novel height loci not previously found in Europeans. We also replicated the European height signals, suggesting that many of the genetic variants that are associated with height are shared between individuals of European and African descent. Finally, in fine-mapping the European height loci in African-ancestry individuals, we found SNPs more likely to be associated with the expression of nearby genes than the SNPs originally found in Europeans. Thus, our results support the utility of performing genetic studies in non-European populations to gain insights into complex human diseases and traits.
Date: 2011
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1002298
DOI: 10.1371/journal.pgen.1002298
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