Title

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Authors

Mariaelisa Graff
Anne E. Justice
Kristin L. Young
Eirini Marouli
Xinruo Zhang
Rebecca S. Fine
Elise Lim
Victoria Buchanan
Kristin Rand
Mary F. Feitosa
Mary K. Wojczynski
Lisa R. Yanek
Yaming Shao
Rebecca Rohde
Adebowale A. Adeyemo
Melinda C. Aldrich
Matthew A. Allison
Christine B. Ambrosone
Stefan Ambs
Christopher Amos
Donna K. Arnett
Larry Atwood
Elisa V. Bandera
Traci Bartz
Diane M. Becker
Sonja I. Berndt
Leslie Bernstein
Lawrence F. Bielak
William J. Blot
Erwin P. Bottinger
Donald W. Bowden
Jonathan P. Bradfield
Jennifer A. Brody
Ulrich Broeckel
Gregory Burke
Brian E. Cade
Qiuyin Cai
Neil Caporaso
Chris Carlson
John Carpten
Graham Casey
Stephen J. Chanock
Guanjie Chen
Minhui Chen
Yii-Der I. Chen
Wei-Min Chen
Alessandra Chesi
Charleston W.K. Chiang
Lisa Chu
Gerry A. Coetzee
David V. Conti
Richard S. Cooper
Mary Cushman
Ellen Demerath
Sandra L. Deming
Latchezar Dimitrov
Jingzhong Ding
W. Ryan Diver
Qing Duan
Michele K. Evans
Adeyinka G. Falusi
Jessica D. Faul
Myriam Fornage
Caroline Fox
Barry I. Freedman
Melissa Garcia
Elizabeth M. Gillanders
Phyllis Goodman
Omri Gottesman
Struan F.A. Grant
Xiuqing Guo
Hakon Hakonarson
Talin Haritunians
Tamara B. Harris
Curtis C. Harris
Brian E. Henderson
Anselm Hennis
Dena G. Hernandez
Joel N. Hirschhorn
Lorna Haughton McNeill
Timothy E. Howard
Barbara Howard
Ann W. Hsing
Yu-Han H. Hsu
Jennifer J. Hu
Chad D. Huff
Dezheng Huo
Sue A. Ingles
Marguerite R. Irvin
Esther M. John
Karen C. Johnson
Joanne M. Jordan
Edmond K. Kabagambe
Sun J. Kang
Sharon L. Kardia
Brendan J. Keating
Rick A. Kittles
Eric A. Klein
Suzanne Kolb
Laurence N. Kolonel
Charles Kooperberg
Lewis Kuller
Abdullah Kutlar
Leslie Lange
Carl D. Langefeld
Loic Le Marchand
Hampton Leonard
Guillaume Lettre
Albert M. Levin, Henry Ford Health SystemFollow
Yun Li
Jin Li
Yongmei Liu
Youfang Liu
Simin Liu
Kurt Lohman
Vaneet Lotay
Yingchang Lu
William Maixner
JoAnn E. Manson
Barbara McKnight
Yan Meng
Keri L. Monda
Kris Monroe
Jason H. Moore
Thomas H. Mosley
Poorva Mudgal
Adam B. Murphy
Rajiv Nadukuru
Mike A. Nalls
Katherine L. Nathanson
Uma Nayak
Amidou N'Diaye
Barbara Nemesure
Christine Neslund-Dudas, Henry Ford Health SystemFollow
Marian L. Neuhouser
Sarah Nyante
Heather Ochs-Balcom
Temidayo O. Ogundiran
Adesola Ogunniyi
Oladosu Ojengbede
Hayrettin Okut
Olufunmilayo I. Olopade
Andrew Olshan
Badri Padhukasahasram, Henry Ford Health Systemn
Julie Palmer
Cameron D. Palmer
Nicholette D. Palmer
George Papanicolaou
Sanjay R. Patel
Curtis A. Pettaway
Patricia A. Peyser
Michael F. Press
D.C. Rao
Laura J. Rasmussen-Torvik
Susan Redline
Alex P. Reiner
Suhn K. Rhie
Jorge L. Rodriguez-Gil
Charles N. Rotimi
Jerome I. Rotter
Edward A. Ruiz-Narvaez
Benjamin A. Rybicki, Henry Ford Health SystemFollow
Babatunde Salako
Michele M. Sale
Maureen Sanderson
Eric Schadt
Pamela J. Schreiner
Claudia Schurmann
Ann G. Schwartz
Daniel A. Shriner
Lisa B. Signorello
Andrew B. Singleton
David S. Siscovick
Jennifer A. Smith
Shad Smith
Elizabeth Speliotes
Margaret Spitz
Janet L. Stanford
Victoria L. Stevens
Alex Stram
Sara S. Strom
Lara Sucheston
Yan V. Sun
Salman M. Tajuddin
Herman Taylor
Kira Taylor
Bamidele O. Tayo
Michael J. Thun
Margaret A. Tucker
Dhananjay Vaidya
David J. Van Den Berg
Sailaja Vedantam
Mara Vitolins
Zhaoming Wang
Erin B. Ware
Sylvia Wassertheil-Smoller
David R. Weir
John K. Wiencke
Scott M. Williams
Keoki L. Williams, Henry Ford Health SystemFollow
James G. Wilson
John S. Witte
Margaret Wrensch
Xifeng Wu
Jie Yao
Neil Zakai
Krista Zanetti
Babette S. Zemel
Wei Zhao
Jing Hua Zhao
Wei Zheng
Degui Zhi
Jie Zhou
Xiaofeng Zhu
Regina G. Ziegler
Joe Zmuda
Alan B. Zonderman
Bruce M. Psaty
Ingrid B. Borecki
L. Adrienne Cupples
Ching-Ti Liu
Christopher A. Haiman
Ruth Loos
Maggie C.Y. Ng
Kari E. North

Document Type

Article

Publication Date

4-1-2021

Publication Title

American journal of human genetics

Abstract

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

PubMed ID

33713608

Volume

108

Issue

4

First Page

564

Last Page

582

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