Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations

Wenlong Carl Chen; Jean Tristan Brandenburg; Ananyo Choudhury; Mahtaab Hayat; Dhriti Sengupta; Yaniv Swiel; Chantal Babb de Villiers; Lucien Ferndale; Colleen Aldous; Cassandra C. Soo; Sang Lee; Charles Curtis; Rob Newton; Tim Waterboer; Freddy Sitas; Debbie Bradshaw; Christian C. Abnet; Michele Ramsay; M. Iqbal Parker; Elvira Singh; Cathryn M. Lewis; Christopher G. Mathew

doi:10.1016/j.ajhg.2023.08.007

Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations

Wenlong Carl Chen, Jean Tristan Brandenburg, Ananyo Choudhury, Mahtaab Hayat, Dhriti Sengupta, Yaniv Swiel, Chantal Babb de Villiers, Lucien Ferndale, Colleen Aldous, Cassandra C. Soo, Sang Lee, Charles Curtis, Rob Newton, Tim Waterboer, Freddy Sitas, Debbie Bradshaw, Christian C. Abnet, Michele Ramsay, M. Iqbal Parker, Elvira SinghCathryn M. Lewis, Christopher G. Mathew^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10⁻⁸, odds ratio = 1.28, 95% confidence interval = 1.22–1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10⁻⁸) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, p_meta = 9.36 × 10⁻¹⁰), chromosome 10 at PLCE1 (rs7099485, p_meta = 1.48 × 10⁻⁸), and chromosome 22 at CHEK2 (rs1033667, p_meta = 1.47 × 10⁻⁹). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

Original language	English
Pages (from-to)	1690-1703
Number of pages	14
Journal	American journal of human genetics
Volume	110
Issue number	10
DOIs	https://doi.org/10.1016/j.ajhg.2023.08.007
Publication status	Published - 5 Oct 2023

Bibliographical note

Funding Information:
This work was supported by the South African Medical Research Council (SAMRC), the National Health Laboratory Service (to E.S.), and the Cancer Association of South Africa (to C.G.M., C.B.dV., and C.M.L.). The Evolving Risk Factors for Cancers in African Populations (ERICA-SA) Study and the Johannesburg Cancer Study were supported by the SAMRC (with funds received from the South African national Department of Health (NDoH) and the UK Medical Research Council (with funds from the UK Government’s Newton Fund ) ( MRCRFA-SHIP 01-2015 ). M.I.P. and C.G.M. were jointly supported by the SAMRC with funds received from the NDOH and the MRC UK with funds from the UK Government’s Newton Fund grant #046 and GSK. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the SAMRC or the South African NDoH or the MRC UK from the UK Government’s Newton Fund . This work was also supported by the following organizations and funding sources: the German Academic Exchange Service-National Research Foundation Joint In-country Scholarship Programme (to W.C.C.); the National Research Foundation and Department of Science and Technology Thuthuka fund (to W.C.C.); the Boehringer Ingelheim Fonds travel grant (to W.C.C.); the Grants, Innovation, and Product Development Unit (GIPD) of the SAMRC ; the National Institute for Health Research Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London (to C.M.L.); and the South African NDoH (to E.S.). We acknowledge the NIH-funded H3Africa Consortium Collaborative Centre , AWI-Gen, for sharing data for the population controls used in our study (PI: M.R.). It is with great sorrow that we record the death of our colleague and co-author Dr. Elvira Singh on 27 February 2022.

Funding Information:
This work was supported by the South African Medical Research Council (SAMRC), the National Health Laboratory Service (to E.S.), and the Cancer Association of South Africa (to C.G.M. C.B.dV. and C.M.L.). The Evolving Risk Factors for Cancers in African Populations (ERICA-SA) Study and the Johannesburg Cancer Study were supported by the SAMRC (with funds received from the South African national Department of Health (NDoH) and the UK Medical Research Council (with funds from the UK Government's Newton Fund) (MRCRFA-SHIP 01-2015). M.I.P. and C.G.M. were jointly supported by the SAMRC with funds received from the NDOH and the MRC UK with funds from the UK Government's Newton Fund grant #046 and GSK. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the SAMRC or the South African NDoH or the MRC UK from the UK Government's Newton Fund. This work was also supported by the following organizations and funding sources: the German Academic Exchange Service-National Research Foundation Joint In-country Scholarship Programme (to W.C.C.); the National Research Foundation and Department of Science and Technology Thuthuka fund (to W.C.C.); the Boehringer Ingelheim Fonds travel grant (to W.C.C.); the Grants, Innovation, and Product Development Unit (GIPD) of the SAMRC; the National Institute for Health Research Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London (to C.M.L.); and the South African NDoH (to E.S.). We acknowledge the NIH-funded H3Africa Consortium Collaborative Centre, AWI-Gen, for sharing data for the population controls used in our study (PI: M.R.). It is with great sorrow that we record the death of our colleague and co-author Dr. Elvira Singh on 27 February 2022. C.G.M. W.C.C. C.M.L. D.B. F.S. and E.S. designed the study. C.G.M. D.B. F.S. E.S. T.W. R.N. C.B.d.V. and C.M.L. acquired the funding. W.C.C. C.B.d.V. L.F. C.S. L.S. C.J.C. F.S. M.R. C.A. M.I.P. and E.S. were responsible for sample acquisition, processing, and management and genotyping. W.C.C. J.T.B. M.H. and Y.S. performed the analysis. W.C.C. and C.G.M. wrote the manuscript. All authors critically reviewed, edited, and approved the manuscript. The authors declare no competing interests.

Publisher Copyright:
© 2023 American Society of Human Genetics

Keywords

African cancer genome-wide association study
ESCC genetics
ESCC GWAS
ESCC meta-analysis
esophageal squamous cell carcinoma

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10.1016/j.ajhg.2023.08.007

Cite this

Chen, W. C., Brandenburg, J. T., Choudhury, A., Hayat, M., Sengupta, D., Swiel, Y., Babb de Villiers, C., Ferndale, L., Aldous, C., Soo, C. C., Lee, S., Curtis, C., Newton, R., Waterboer, T., Sitas, F., Bradshaw, D., Abnet, C. C., Ramsay, M., Parker, M. I., ... Mathew, C. G. (2023). Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations. American journal of human genetics, 110(10), 1690-1703. https://doi.org/10.1016/j.ajhg.2023.08.007

@article{8e8bdf031715410c87cd3dda6defb37b,

title = "Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations",

abstract = "Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10−8, odds ratio = 1.28, 95% confidence interval = 1.22–1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10−8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10−10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10−8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10−9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.",

keywords = "African cancer genome-wide association study, ESCC genetics, ESCC GWAS, ESCC meta-analysis, esophageal squamous cell carcinoma",

author = "Chen, {Wenlong Carl} and Brandenburg, {Jean Tristan} and Ananyo Choudhury and Mahtaab Hayat and Dhriti Sengupta and Yaniv Swiel and {Babb de Villiers}, Chantal and Lucien Ferndale and Colleen Aldous and Soo, {Cassandra C.} and Sang Lee and Charles Curtis and Rob Newton and Tim Waterboer and Freddy Sitas and Debbie Bradshaw and Abnet, {Christian C.} and Michele Ramsay and Parker, {M. Iqbal} and Elvira Singh and Lewis, {Cathryn M.} and Mathew, {Christopher G.}",

note = "Funding Information: This work was supported by the South African Medical Research Council (SAMRC), the National Health Laboratory Service (to E.S.), and the Cancer Association of South Africa (to C.G.M., C.B.dV., and C.M.L.). The Evolving Risk Factors for Cancers in African Populations (ERICA-SA) Study and the Johannesburg Cancer Study were supported by the SAMRC (with funds received from the South African national Department of Health (NDoH) and the UK Medical Research Council (with funds from the UK Government{\textquoteright}s Newton Fund ) ( MRCRFA-SHIP 01-2015 ). M.I.P. and C.G.M. were jointly supported by the SAMRC with funds received from the NDOH and the MRC UK with funds from the UK Government{\textquoteright}s Newton Fund grant #046 and GSK. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the SAMRC or the South African NDoH or the MRC UK from the UK Government{\textquoteright}s Newton Fund . This work was also supported by the following organizations and funding sources: the German Academic Exchange Service-National Research Foundation Joint In-country Scholarship Programme (to W.C.C.); the National Research Foundation and Department of Science and Technology Thuthuka fund (to W.C.C.); the Boehringer Ingelheim Fonds travel grant (to W.C.C.); the Grants, Innovation, and Product Development Unit (GIPD) of the SAMRC ; the National Institute for Health Research Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London (to C.M.L.); and the South African NDoH (to E.S.). We acknowledge the NIH-funded H3Africa Consortium Collaborative Centre , AWI-Gen, for sharing data for the population controls used in our study (PI: M.R.). It is with great sorrow that we record the death of our colleague and co-author Dr. Elvira Singh on 27 February 2022. Funding Information: This work was supported by the South African Medical Research Council (SAMRC), the National Health Laboratory Service (to E.S.), and the Cancer Association of South Africa (to C.G.M. C.B.dV. and C.M.L.). The Evolving Risk Factors for Cancers in African Populations (ERICA-SA) Study and the Johannesburg Cancer Study were supported by the SAMRC (with funds received from the South African national Department of Health (NDoH) and the UK Medical Research Council (with funds from the UK Government's Newton Fund) (MRCRFA-SHIP 01-2015). M.I.P. and C.G.M. were jointly supported by the SAMRC with funds received from the NDOH and the MRC UK with funds from the UK Government's Newton Fund grant #046 and GSK. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the SAMRC or the South African NDoH or the MRC UK from the UK Government's Newton Fund. This work was also supported by the following organizations and funding sources: the German Academic Exchange Service-National Research Foundation Joint In-country Scholarship Programme (to W.C.C.); the National Research Foundation and Department of Science and Technology Thuthuka fund (to W.C.C.); the Boehringer Ingelheim Fonds travel grant (to W.C.C.); the Grants, Innovation, and Product Development Unit (GIPD) of the SAMRC; the National Institute for Health Research Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London (to C.M.L.); and the South African NDoH (to E.S.). We acknowledge the NIH-funded H3Africa Consortium Collaborative Centre, AWI-Gen, for sharing data for the population controls used in our study (PI: M.R.). It is with great sorrow that we record the death of our colleague and co-author Dr. Elvira Singh on 27 February 2022. C.G.M. W.C.C. C.M.L. D.B. F.S. and E.S. designed the study. C.G.M. D.B. F.S. E.S. T.W. R.N. C.B.d.V. and C.M.L. acquired the funding. W.C.C. C.B.d.V. L.F. C.S. L.S. C.J.C. F.S. M.R. C.A. M.I.P. and E.S. were responsible for sample acquisition, processing, and management and genotyping. W.C.C. J.T.B. M.H. and Y.S. performed the analysis. W.C.C. and C.G.M. wrote the manuscript. All authors critically reviewed, edited, and approved the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2023 American Society of Human Genetics",

year = "2023",

month = oct,

day = "5",

doi = "10.1016/j.ajhg.2023.08.007",

language = "English",

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Chen, WC, Brandenburg, JT, Choudhury, A, Hayat, M, Sengupta, D, Swiel, Y, Babb de Villiers, C, Ferndale, L, Aldous, C, Soo, CC, Lee, S, Curtis, C, Newton, R, Waterboer, T, Sitas, F, Bradshaw, D, Abnet, CC, Ramsay, M, Parker, MI, Singh, E, Lewis, CM & Mathew, CG 2023, 'Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations', American journal of human genetics, vol. 110, no. 10, pp. 1690-1703. https://doi.org/10.1016/j.ajhg.2023.08.007

Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations. / Chen, Wenlong Carl; Brandenburg, Jean Tristan; Choudhury, Ananyo et al.
In: American journal of human genetics, Vol. 110, No. 10, 05.10.2023, p. 1690-1703.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations

AU - Chen, Wenlong Carl

AU - Brandenburg, Jean Tristan

AU - Choudhury, Ananyo

AU - Hayat, Mahtaab

AU - Sengupta, Dhriti

AU - Swiel, Yaniv

AU - Babb de Villiers, Chantal

AU - Ferndale, Lucien

AU - Aldous, Colleen

AU - Soo, Cassandra C.

AU - Lee, Sang

AU - Curtis, Charles

AU - Newton, Rob

AU - Waterboer, Tim

AU - Sitas, Freddy

AU - Bradshaw, Debbie

AU - Abnet, Christian C.

AU - Ramsay, Michele

AU - Parker, M. Iqbal

AU - Singh, Elvira

AU - Lewis, Cathryn M.

AU - Mathew, Christopher G.

N1 - Funding Information: This work was supported by the South African Medical Research Council (SAMRC), the National Health Laboratory Service (to E.S.), and the Cancer Association of South Africa (to C.G.M., C.B.dV., and C.M.L.). The Evolving Risk Factors for Cancers in African Populations (ERICA-SA) Study and the Johannesburg Cancer Study were supported by the SAMRC (with funds received from the South African national Department of Health (NDoH) and the UK Medical Research Council (with funds from the UK Government’s Newton Fund ) ( MRCRFA-SHIP 01-2015 ). M.I.P. and C.G.M. were jointly supported by the SAMRC with funds received from the NDOH and the MRC UK with funds from the UK Government’s Newton Fund grant #046 and GSK. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the SAMRC or the South African NDoH or the MRC UK from the UK Government’s Newton Fund . This work was also supported by the following organizations and funding sources: the German Academic Exchange Service-National Research Foundation Joint In-country Scholarship Programme (to W.C.C.); the National Research Foundation and Department of Science and Technology Thuthuka fund (to W.C.C.); the Boehringer Ingelheim Fonds travel grant (to W.C.C.); the Grants, Innovation, and Product Development Unit (GIPD) of the SAMRC ; the National Institute for Health Research Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London (to C.M.L.); and the South African NDoH (to E.S.). We acknowledge the NIH-funded H3Africa Consortium Collaborative Centre , AWI-Gen, for sharing data for the population controls used in our study (PI: M.R.). It is with great sorrow that we record the death of our colleague and co-author Dr. Elvira Singh on 27 February 2022. Funding Information: This work was supported by the South African Medical Research Council (SAMRC), the National Health Laboratory Service (to E.S.), and the Cancer Association of South Africa (to C.G.M. C.B.dV. and C.M.L.). The Evolving Risk Factors for Cancers in African Populations (ERICA-SA) Study and the Johannesburg Cancer Study were supported by the SAMRC (with funds received from the South African national Department of Health (NDoH) and the UK Medical Research Council (with funds from the UK Government's Newton Fund) (MRCRFA-SHIP 01-2015). M.I.P. and C.G.M. were jointly supported by the SAMRC with funds received from the NDOH and the MRC UK with funds from the UK Government's Newton Fund grant #046 and GSK. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the SAMRC or the South African NDoH or the MRC UK from the UK Government's Newton Fund. This work was also supported by the following organizations and funding sources: the German Academic Exchange Service-National Research Foundation Joint In-country Scholarship Programme (to W.C.C.); the National Research Foundation and Department of Science and Technology Thuthuka fund (to W.C.C.); the Boehringer Ingelheim Fonds travel grant (to W.C.C.); the Grants, Innovation, and Product Development Unit (GIPD) of the SAMRC; the National Institute for Health Research Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London (to C.M.L.); and the South African NDoH (to E.S.). We acknowledge the NIH-funded H3Africa Consortium Collaborative Centre, AWI-Gen, for sharing data for the population controls used in our study (PI: M.R.). It is with great sorrow that we record the death of our colleague and co-author Dr. Elvira Singh on 27 February 2022. C.G.M. W.C.C. C.M.L. D.B. F.S. and E.S. designed the study. C.G.M. D.B. F.S. E.S. T.W. R.N. C.B.d.V. and C.M.L. acquired the funding. W.C.C. C.B.d.V. L.F. C.S. L.S. C.J.C. F.S. M.R. C.A. M.I.P. and E.S. were responsible for sample acquisition, processing, and management and genotyping. W.C.C. J.T.B. M.H. and Y.S. performed the analysis. W.C.C. and C.G.M. wrote the manuscript. All authors critically reviewed, edited, and approved the manuscript. The authors declare no competing interests. Publisher Copyright: © 2023 American Society of Human Genetics

PY - 2023/10/5

Y1 - 2023/10/5

N2 - Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10−8, odds ratio = 1.28, 95% confidence interval = 1.22–1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10−8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10−10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10−8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10−9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

AB - Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10−8, odds ratio = 1.28, 95% confidence interval = 1.22–1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10−8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10−10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10−8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10−9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

KW - African cancer genome-wide association study

KW - ESCC genetics

KW - ESCC GWAS

KW - ESCC meta-analysis

KW - esophageal squamous cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85173447675&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2023.08.007

DO - 10.1016/j.ajhg.2023.08.007

M3 - Article

C2 - 37673066

AN - SCOPUS:85173447675

SN - 0002-9297

VL - 110

SP - 1690

EP - 1703

JO - American journal of human genetics

JF - American journal of human genetics

IS - 10

ER -

Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations

Abstract

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