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Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry

N'Diaye, A and Chen, GK and Palmer, CD and Ge, B and Tayo, B and Mathias, RA and Ding, J and Nalls, MA and Adeyemo, A and Adoue, V and Ambrosone, CB and Atwood, L and Bandera, EV and Becker, LC and Berndt, SI and Bernstein, L and Blot, WJ and Boerwinkle, E and Britton, A and Casey, G and Chanock, SJ and Demerath, E and Deming, SL and Diver, WR and Fox, C and Harris, TB and Hernandez, DG and Hu, JJ and Ingles, SA and John, EM and Johnson, C and Keating, B and Kittles, RA and Kolonel, LN and Kritchevsky, SB and Marchand, L and Lohman, K and Liu, J and Millikan, RC and Murphy, A and Musani, S and Neslund-Dudas, C and North, KE and Nyante, S and Ogunniyi, A and Ostrander, EA and Papanicolaou, G and Patel, S and Pettaway, CA and Press, MF and Redline, S and Rodriguez-Gil, JL and Rotimi, C and Rybicki, BA and Salako, B and Schreiner, PJ and Signorello, LB and Singleton, AB and Stanford, JL and Stram, AH and Stram, DO and Strom, SS and Suktitipat, B and Thun, MJ and Witte, JS and Yanek, LR and Ziegler, RG and Zheng, W and Zhu, X and Zmuda, JM and Zonderman, AB and Evans, MK and Liu, Y and Becker, DM and Cooper, RS and Pastinen, T and Henderson, BE and Hirschhorn, JN and Lettre, G and Haiman, CA (2011) Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry. PLoS Genetics, 7 (10). ISSN 1553-7390

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Abstract

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. © 2011 N'Diaye et al.


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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
N'Diaye, A
Chen, GK
Palmer, CD
Ge, B
Tayo, B
Mathias, RA
Ding, J
Nalls, MA
Adeyemo, A
Adoue, V
Ambrosone, CB
Atwood, L
Bandera, EV
Becker, LC
Berndt, SI
Bernstein, L
Blot, WJ
Boerwinkle, E
Britton, A
Casey, G
Chanock, SJ
Demerath, E
Deming, SL
Diver, WR
Fox, C
Harris, TB
Hernandez, DG
Hu, JJ
Ingles, SA
John, EM
Johnson, C
Keating, B
Kittles, RA
Kolonel, LN
Kritchevsky, SB
Marchand, L
Lohman, K
Liu, J
Millikan, RC
Murphy, A
Musani, S
Neslund-Dudas, C
North, KE
Nyante, S
Ogunniyi, A
Ostrander, EA
Papanicolaou, G
Patel, S
Pettaway, CA
Press, MF
Redline, S
Rodriguez-Gil, JL
Rotimi, C
Rybicki, BA
Salako, B
Schreiner, PJ
Signorello, LB
Singleton, AB
Stanford, JL
Stram, AH
Stram, DO
Strom, SS
Suktitipat, B
Thun, MJ
Witte, JS
Yanek, LR
Ziegler, RG
Zheng, W
Zhu, X
Zmuda, JMZmudaJ@edc.pitt.eduEPIDJMZ
Zonderman, AB
Evans, MK
Liu, Y
Becker, DM
Cooper, RS
Pastinen, T
Henderson, BE
Hirschhorn, JN
Lettre, G
Haiman, CA
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorVisscher, Peter M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 October 2011
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 7
Number: 10
DOI or Unique Handle: 10.1371/journal.pgen.1002298
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 1553-7390
MeSH Headings: Adult; African Americans--genetics; Aged; Aged, 80 and over; Body Height--genetics; Chromosome Mapping; European Continental Ancestry Group--genetics; Female; Gene Frequency; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide
Other ID: NLM PMC3188544
PubMed Central ID: PMC3188544
PubMed ID: 21998595
Date Deposited: 10 Sep 2012 14:21
Last Modified: 05 Feb 2019 00:55
URI: http://d-scholarship.pitt.edu/id/eprint/13980

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