Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium

Lindsay Fernández-Rhodes; Mariaelisa Graff; Victoria L. Buchanan; Anne E. Justice; Heather M. Highland; Xiuqing Guo; Wanying Zhu; Hung Hsin Chen; Kristin L. Young; Kaustubh Adhikari; Nicholette D. Palmer; Jennifer E. Below; Jonathan Bradfield; Alexandre C. Pereira; LáShauntá S. Glover; Daeeun Kim; Adam G. Lilly; Poojan Shrestha; Alvin G. Thomas; Xinruo Zhang; Minhui Chen; Charleston W.K. Chiang; Sara Pulit; Andrea Horimoto; Jose E. Krieger; Marta Guindo-Martínez; Michael Preuss; Claudia Schumann; Roelof A.J. Smit; Gabriela Torres-Mejía; Victor Acuña-Alonzo; Gabriel Bedoya; Maria Cátira Bortolini; Samuel Canizales-Quinteros; Carla Gallo; Rolando González-José; Giovanni Poletti; Francisco Rothhammer; Hakon Hakonarson; Robert Igo; Sharon G. Adler; Sudha K. Iyengar; Susanne B. Nicholas; Stephanie M. Gogarten; Carmen R. Isasi; George Papnicolaou; Adrienne M. Stilp; Qibin Qi; Minjung Kho; Jennifer A. Smith; Carl D. Langefeld; Lynne Wagenknecht; Roberta Mckean-Cowdin; Xiaoyi Raymond Gao; Darryl Nousome; David V. Conti; Ye Feng; Matthew A. Allison; Zorayr Arzumanyan; Thomas A. Buchanan; Yii Der Ida Chen; Pauline M. Genter; Mark O. Goodarzi; Yang Hai; Willa Hsueh; Eli Ipp; Fouad R. Kandeel; Kelvin Lam; Xiaohui Li; Jerry L. Nadler; Leslie J. Raffel; Kathryn Roll; Kevin Sandow; Jingyi Tan; Kent D. Taylor; Anny H. Xiang; Jie Yao; Astride Audirac-Chalifour; Jose de Jesus Peralta Romero; Fernando Hartwig; Bernando Horta; John Blangero; Joanne E. Curran; Ravindranath Duggirala; Donna E. Lehman; Sobha Puppala; Laura Fejerman; Esther M. John; Carlos Aguilar-Salinas; Noël P. Burtt; Jose C. Florez; Humberto García-Ortíz; Clicerio González-Villalpando; Josep Mercader; Lorena Orozco; Teresa Tusié-Luna; Estela Blanco; Sheila Gahagan; Nancy J. Cox; Craig Hanis; Nancy F. Butte; Shelley A. Cole; Anthony G. Comuzzie; V. Saroja Voruganti; Rebecca Rohde; Yujie Wang; Tamar Sofer; Elad Ziv; Struan F.A. Grant; Andres Ruiz-Linares; Jerome I. Rotter; Christopher A. Haiman; Esteban J. Parra; Miguel Cruz; Ruth J.F. Loos; Kari E. North

doi:10.1016/j.xhgg.2022.100099

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium

Lindsay Fernández-Rhodes, Mariaelisa Graff, Victoria L. Buchanan, Anne E. Justice, Heather M. Highland, Xiuqing Guo, Wanying Zhu, Hung Hsin Chen, Kristin L. Young, Kaustubh Adhikari, Nicholette D. Palmer, Jennifer E. Below, Jonathan Bradfield, Alexandre C. Pereira, LáShauntá S. Glover, Daeeun Kim, Adam G. Lilly, Poojan Shrestha, Alvin G. Thomas, Xinruo ZhangMinhui Chen, Charleston W.K. Chiang, Sara Pulit, Andrea Horimoto, Jose E. Krieger, Marta Guindo-Martínez, Michael Preuss, Claudia Schumann, Roelof A.J. Smit, Gabriela Torres-Mejía, Victor Acuña-Alonzo, Gabriel Bedoya, Maria Cátira Bortolini, Samuel Canizales-Quinteros, Carla Gallo, Rolando González-José, Giovanni Poletti, Francisco Rothhammer, Hakon Hakonarson, Robert Igo, Sharon G. Adler, Sudha K. Iyengar, Susanne B. Nicholas, Stephanie M. Gogarten, Carmen R. Isasi, George Papnicolaou, Adrienne M. Stilp, Qibin Qi, Minjung Kho, Jennifer A. Smith, Carl D. Langefeld, Lynne Wagenknecht, Roberta Mckean-Cowdin, Xiaoyi Raymond Gao, Darryl Nousome, David V. Conti, Ye Feng, Matthew A. Allison, Zorayr Arzumanyan, Thomas A. Buchanan, Yii Der Ida Chen, Pauline M. Genter, Mark O. Goodarzi, Yang Hai, Willa Hsueh, Eli Ipp, Fouad R. Kandeel, Kelvin Lam, Xiaohui Li, Jerry L. Nadler, Leslie J. Raffel, Kathryn Roll, Kevin Sandow, Jingyi Tan, Kent D. Taylor, Anny H. Xiang, Jie Yao, Astride Audirac-Chalifour, Jose de Jesus Peralta Romero, Fernando Hartwig, Bernando Horta, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Donna E. Lehman, Sobha Puppala, Laura Fejerman, Esther M. John, Carlos Aguilar-Salinas, Noël P. Burtt, Jose C. Florez, Humberto García-Ortíz, Clicerio González-Villalpando, Josep Mercader, Lorena Orozco, Teresa Tusié-Luna, Estela Blanco, Sheila Gahagan, Nancy J. Cox, Craig Hanis, Nancy F. Butte, Shelley A. Cole, Anthony G. Comuzzie, V. Saroja Voruganti, Rebecca Rohde, Yujie Wang, Tamar Sofer, Elad Ziv, Struan F.A. Grant, Andres Ruiz-Linares, Jerome I. Rotter, Christopher A. Haiman, Esteban J. Parra, Miguel Cruz, Ruth J.F. Loos, Kari E. North

Resultado de la investigación: Article › revisión exhaustiva

4 Citas (Scopus)

Resumen

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Idioma original	English (US)
Número de artículo	100099
Publicación	Human Genetics and Genomics Advances
Volumen	3
N.º	2
DOI	https://doi.org/10.1016/j.xhgg.2022.100099
Estado	Published - abr 14 2022

ASJC Scopus subject areas

Genetics(clinical)
Molecular Medicine

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10.1016/j.xhgg.2022.100099

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Fernández-Rhodes, L., Graff, M., Buchanan, V. L., Justice, A. E., Highland, H. M., Guo, X., Zhu, W., Chen, H. H., Young, K. L., Adhikari, K., Palmer, N. D., Below, J. E., Bradfield, J., Pereira, A. C., Glover, L. S., Kim, D., Lilly, A. G., Shrestha, P., Thomas, A. G., ... North, K. E. (2022). Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium. Human Genetics and Genomics Advances, 3(2), [100099]. https://doi.org/10.1016/j.xhgg.2022.100099

Fernández-Rhodes, L, Graff, M, Buchanan, VL, Justice, AE, Highland, HM, Guo, X, Zhu, W, Chen, HH, Young, KL, Adhikari, K, Palmer, ND, Below, JE, Bradfield, J, Pereira, AC, Glover, LS, Kim, D, Lilly, AG, Shrestha, P, Thomas, AG, Zhang, X, Chen, M, Chiang, CWK, Pulit, S, Horimoto, A, Krieger, JE, Guindo-Martínez, M, Preuss, M, Schumann, C, Smit, RAJ, Torres-Mejía, G, Acuña-Alonzo, V, Bedoya, G, Bortolini, MC, Canizales-Quinteros, S, Gallo, C, González-José, R, Poletti, G, Rothhammer, F, Hakonarson, H, Igo, R, Adler, SG, Iyengar, SK, Nicholas, SB, Gogarten, SM, Isasi, CR, Papnicolaou, G, Stilp, AM, Qi, Q, Kho, M, Smith, JA, Langefeld, CD, Wagenknecht, L, Mckean-Cowdin, R, Gao, XR, Nousome, D, Conti, DV, Feng, Y, Allison, MA, Arzumanyan, Z, Buchanan, TA, Ida Chen, YD, Genter, PM, Goodarzi, MO, Hai, Y, Hsueh, W, Ipp, E, Kandeel, FR, Lam, K, Li, X, Nadler, JL, Raffel, LJ, Roll, K, Sandow, K, Tan, J, Taylor, KD, Xiang, AH, Yao, J, Audirac-Chalifour, A, de Jesus Peralta Romero, J, Hartwig, F, Horta, B, Blangero, J, Curran, JE, Duggirala, R, Lehman, DE, Puppala, S, Fejerman, L, John, EM, Aguilar-Salinas, C, Burtt, NP, Florez, JC, García-Ortíz, H, González-Villalpando, C, Mercader, J, Orozco, L, Tusié-Luna, T, Blanco, E, Gahagan, S, Cox, NJ, Hanis, C, Butte, NF, Cole, SA, Comuzzie, AG, Voruganti, VS, Rohde, R, Wang, Y, Sofer, T, Ziv, E, Grant, SFA, Ruiz-Linares, A, Rotter, JI, Haiman, CA, Parra, EJ, Cruz, M, Loos, RJF & North, KE 2022, 'Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium', Human Genetics and Genomics Advances, vol. 3, n.º 2, 100099. https://doi.org/10.1016/j.xhgg.2022.100099

@article{6055def9aa4e4c32bcdf09dee064b185,

title = "Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium",

abstract = "Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.",

keywords = "Hispanic/Latino, anthropometrics, diversity, fine-mapping, obesity, population stratification, trans-ancestral or trans-ethnic",

author = "Lindsay Fern{\'a}ndez-Rhodes and Mariaelisa Graff and Buchanan, {Victoria L.} and Justice, {Anne E.} and Highland, {Heather M.} and Xiuqing Guo and Wanying Zhu and Chen, {Hung Hsin} and Young, {Kristin L.} and Kaustubh Adhikari and Palmer, {Nicholette D.} and Below, {Jennifer E.} and Jonathan Bradfield and Pereira, {Alexandre C.} and Glover, {L{\'a}Shaunt{\'a} S.} and Daeeun Kim and Lilly, {Adam G.} and Poojan Shrestha and Thomas, {Alvin G.} and Xinruo Zhang and Minhui Chen and Chiang, {Charleston W.K.} and Sara Pulit and Andrea Horimoto and Krieger, {Jose E.} and Marta Guindo-Mart{\'i}nez and Michael Preuss and Claudia Schumann and Smit, {Roelof A.J.} and Gabriela Torres-Mej{\'i}a and Victor Acu{\~n}a-Alonzo and Gabriel Bedoya and Bortolini, {Maria C{\'a}tira} and Samuel Canizales-Quinteros and Carla Gallo and Rolando Gonz{\'a}lez-Jos{\'e} and Giovanni Poletti and Francisco Rothhammer and Hakon Hakonarson and Robert Igo and Adler, {Sharon G.} and Iyengar, {Sudha K.} and Nicholas, {Susanne B.} and Gogarten, {Stephanie M.} and Isasi, {Carmen R.} and George Papnicolaou and Stilp, {Adrienne M.} and Qibin Qi and Minjung Kho and Smith, {Jennifer A.} and Langefeld, {Carl D.} and Lynne Wagenknecht and Roberta Mckean-Cowdin and Gao, {Xiaoyi Raymond} and Darryl Nousome and Conti, {David V.} and Ye Feng and Allison, {Matthew A.} and Zorayr Arzumanyan and Buchanan, {Thomas A.} and {Ida Chen}, {Yii Der} and Genter, {Pauline M.} and Goodarzi, {Mark O.} and Yang Hai and Willa Hsueh and Eli Ipp and Kandeel, {Fouad R.} and Kelvin Lam and Xiaohui Li and Nadler, {Jerry L.} and Raffel, {Leslie J.} and Kathryn Roll and Kevin Sandow and Jingyi Tan and Taylor, {Kent D.} and Xiang, {Anny H.} and Jie Yao and Astride Audirac-Chalifour and {de Jesus Peralta Romero}, Jose and Fernando Hartwig and Bernando Horta and John Blangero and Curran, {Joanne E.} and Ravindranath Duggirala and Lehman, {Donna E.} and Sobha Puppala and Laura Fejerman and John, {Esther M.} and Carlos Aguilar-Salinas and Burtt, {No{\"e}l P.} and Florez, {Jose C.} and Humberto Garc{\'i}a-Ort{\'i}z and Clicerio Gonz{\'a}lez-Villalpando and Josep Mercader and Lorena Orozco and Teresa Tusi{\'e}-Luna and Estela Blanco and Sheila Gahagan and Cox, {Nancy J.} and Craig Hanis and Butte, {Nancy F.} and Cole, {Shelley A.} and Comuzzie, {Anthony G.} and Voruganti, {V. Saroja} and Rebecca Rohde and Yujie Wang and Tamar Sofer and Elad Ziv and Grant, {Struan F.A.} and Andres Ruiz-Linares and Rotter, {Jerome I.} and Haiman, {Christopher A.} and Parra, {Esteban J.} and Miguel Cruz and Loos, {Ruth J.F.} and North, {Kari E.}",

note = "Funding Information: S.M.G. and A.M.S. receive funding from Seven Bridges Genomics to develop tools for the NHLBI BioData Catalyst consortium. All others authors declare no competing interests. Funding Information: A.G.L. was supported by NIH (T32 HD091058, P2C HD050924, and P30 AG066615). A.G.T. was supported by NIH (T32HL007055). A.R.L. has been supported by the Leverhulme Trust (F/07 134/DF), the Excellence Initiative of Aix-Marseille University - A?MIDEX (a French ?Investissements d'Avenir? programme), the National Natural Science Foundation of China (#31771393), the Scientific and Technology Committee of Shanghai Municipality (18490750300), Ministry of Science and Technology of China (2020YFE0201600), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the 111 Project (B13016), and BBSRC (BB/I021213/1). L.F. was supported by NIH (R01CA204797). L.F.-R. was supported by an American Heart Association predoctoral grant (13PRE16100015). M.G. K.L.Y. and K.E.N. were supported by AHA (13GRNT16490017, 15GRNT25880008), R01DK089256, and R01DK101855. L.F.-R. C.A.H. and R.F.J.L. were supported by NIH (R01DK101855). X.R.G. was supported by NIH (R01EY022651). K.E.N. was supported by NIH (R01HD057194, R01DK122503, R01HG010297, R01HL142302, R01HL143885, and R01HG009974). L.G. was supported by NIH (T32 HL129982). Q.Q. was supported by NIH (R01HL060712, R01HL140976, and R01DK119268). S.F.A.G. was supported by the Daniel B. Burke Endowed Chair for Diabetes Research and NIH (R01 HD056465). X.G. M.A.A. Y.-D.I.C. J.Y. and J.I.R. were supported by NIH (EY14684, HL-0767711, HL-0697974, HL-088457, NEI EY11753, UL1-TR-001881). X.L. and K.R. were supported by NIH (R01 HL0767711 and DK-079888). Z.A. T.A.B. J.T. and A.H.X. were supported by HTN-IR funding (HL-0697974) and P.M.G. Y.H. E.I. and K.D.T. were supported by NIH (EY-14684). M.O.G. W.H. K.L. and K.S. were supported by NIH (HL-088457). A.E.J. was supported by NIH (K99/R00 HL130580). E.M.J. was supported by NIH (R01 CA063446, R01 CA077305, DOD RP9590546, and CBCRP 7PB-0068). J.M. was supported by the American Diabetes Association 1-19-ICTS-068 and by U01HG011723. C.W.K.C. was supported by R35GM142783. Study-specific acknowledgments are available as supplemental data. S.M.G. and A.M.S. receive funding from Seven Bridges Genomics to develop tools for the NHLBI BioData Catalyst consortium. All others authors declare no competing interests. Funding Information: A.G.L. was supported by NIH ( T32 HD091058 , P2C HD050924 , and P30 AG066615 ). A.G.T. was supported by NIH ( T32HL007055 ). A.R.L. has been supported by the Leverhulme Trust ( F/07 134/DF ), the Excellence Initiative of Aix-Marseille University - A∗MIDEX (a French “Investissements d{\textquoteright}Avenir” programme), the National Natural Science Foundation of China ( #31771393 ), the Scientific and Technology Committee of Shanghai Municipality ( 18490750300 ), Ministry of Science and Technology of China ( 2020YFE0201600 ), Shanghai Municipal Science and Technology Major Project ( 2017SHZDZX01 ), the 111 Project ( B13016 ), and BBSRC ( BB/I021213/1 ). L.F. was supported by NIH ( R01CA204797 ). L.F.-R. was supported by an American Heart Association predoctoral grant ( 13PRE16100015 ). M.G., K.L.Y., and K.E.N. were supported by AHA ( 13GRNT16490017 , 15GRNT25880008 ), R01DK089256 , and R01DK101855 . L.F.-R., C.A.H., and R.F.J.L. were supported by NIH ( R01DK101855 ). X.R.G. was supported by NIH ( R01EY022651 ). K.E.N. was supported by NIH ( R01HD057194 , R01DK122503 , R01HG010297 , R01HL142302 , R01HL143885 , and R01HG009974 ). L.G. was supported by NIH ( T32 HL129982 ). Q.Q. was supported by NIH ( R01HL060712 , R01HL140976 , and R01DK119268 ). S.F.A.G. was supported by the Daniel B. Burke Endowed Chair for Diabetes Research and NIH ( R01 HD056465 ). X.G., M.A.A., Y.-D.I.C., J.Y., and J.I.R. were supported by NIH ( EY14684 , HL-0767711 , HL-0697974 , HL-088457 , NEI EY11753 , UL1-TR-001881 ). X.L. and K.R. were supported by NIH ( R01 HL0767711 and DK-079888 ). Z.A., T.A.B., J.T., and A.H.X. were supported by HTN-IR funding ( HL-0697974 ) and P.M.G., Y.H., E.I., and K.D.T. were supported by NIH ( EY-14684 ). M.O.G., W.H., K.L., and K.S. were supported by NIH ( HL-088457 ). A.E.J. was supported by NIH ( K99/R00 HL130580 ). E.M.J. was supported by NIH ( R01 CA063446 , R01 CA077305 , DOD RP9590546 , and CBCRP 7PB-0068 ). J.M. was supported by the American Diabetes Association 1-19-ICTS-068 and by U01HG011723 . C.W.K.C. was supported by R35GM142783 . Study-specific acknowledgments are available as supplemental data . Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = apr,

day = "14",

doi = "10.1016/j.xhgg.2022.100099",

language = "English (US)",

volume = "3",

journal = "Human Genetics and Genomics Advances",

issn = "2666-2477",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium

AU - Fernández-Rhodes, Lindsay

AU - Graff, Mariaelisa

AU - Buchanan, Victoria L.

AU - Justice, Anne E.

AU - Highland, Heather M.

AU - Guo, Xiuqing

AU - Zhu, Wanying

AU - Chen, Hung Hsin

AU - Young, Kristin L.

AU - Adhikari, Kaustubh

AU - Palmer, Nicholette D.

AU - Below, Jennifer E.

AU - Bradfield, Jonathan

AU - Pereira, Alexandre C.

AU - Glover, LáShauntá S.

AU - Kim, Daeeun

AU - Lilly, Adam G.

AU - Shrestha, Poojan

AU - Thomas, Alvin G.

AU - Zhang, Xinruo

AU - Chen, Minhui

AU - Chiang, Charleston W.K.

AU - Pulit, Sara

AU - Horimoto, Andrea

AU - Krieger, Jose E.

AU - Guindo-Martínez, Marta

AU - Preuss, Michael

AU - Schumann, Claudia

AU - Smit, Roelof A.J.

AU - Torres-Mejía, Gabriela

AU - Acuña-Alonzo, Victor

AU - Bedoya, Gabriel

AU - Bortolini, Maria Cátira

AU - Canizales-Quinteros, Samuel

AU - Gallo, Carla

AU - González-José, Rolando

AU - Poletti, Giovanni

AU - Rothhammer, Francisco

AU - Hakonarson, Hakon

AU - Igo, Robert

AU - Adler, Sharon G.

AU - Iyengar, Sudha K.

AU - Nicholas, Susanne B.

AU - Gogarten, Stephanie M.

AU - Isasi, Carmen R.

AU - Papnicolaou, George

AU - Stilp, Adrienne M.

AU - Qi, Qibin

AU - Kho, Minjung

AU - Smith, Jennifer A.

AU - Langefeld, Carl D.

AU - Wagenknecht, Lynne

AU - Mckean-Cowdin, Roberta

AU - Gao, Xiaoyi Raymond

AU - Nousome, Darryl

AU - Conti, David V.

AU - Feng, Ye

AU - Allison, Matthew A.

AU - Arzumanyan, Zorayr

AU - Buchanan, Thomas A.

AU - Ida Chen, Yii Der

AU - Genter, Pauline M.

AU - Goodarzi, Mark O.

AU - Hai, Yang

AU - Hsueh, Willa

AU - Ipp, Eli

AU - Kandeel, Fouad R.

AU - Lam, Kelvin

AU - Li, Xiaohui

AU - Nadler, Jerry L.

AU - Raffel, Leslie J.

AU - Roll, Kathryn

AU - Sandow, Kevin

AU - Tan, Jingyi

AU - Taylor, Kent D.

AU - Xiang, Anny H.

AU - Yao, Jie

AU - Audirac-Chalifour, Astride

AU - de Jesus Peralta Romero, Jose

AU - Hartwig, Fernando

AU - Horta, Bernando

AU - Blangero, John

AU - Curran, Joanne E.

AU - Duggirala, Ravindranath

AU - Lehman, Donna E.

AU - Puppala, Sobha

AU - Fejerman, Laura

AU - John, Esther M.

AU - Aguilar-Salinas, Carlos

AU - Burtt, Noël P.

AU - Florez, Jose C.

AU - García-Ortíz, Humberto

AU - González-Villalpando, Clicerio

AU - Mercader, Josep

AU - Orozco, Lorena

AU - Tusié-Luna, Teresa

AU - Blanco, Estela

AU - Gahagan, Sheila

AU - Cox, Nancy J.

AU - Hanis, Craig

AU - Butte, Nancy F.

AU - Cole, Shelley A.

AU - Comuzzie, Anthony G.

AU - Voruganti, V. Saroja

AU - Rohde, Rebecca

AU - Wang, Yujie

AU - Sofer, Tamar

AU - Ziv, Elad

AU - Grant, Struan F.A.

AU - Ruiz-Linares, Andres

AU - Rotter, Jerome I.

AU - Haiman, Christopher A.

AU - Parra, Esteban J.

AU - Cruz, Miguel

AU - Loos, Ruth J.F.

AU - North, Kari E.

N1 - Funding Information: S.M.G. and A.M.S. receive funding from Seven Bridges Genomics to develop tools for the NHLBI BioData Catalyst consortium. All others authors declare no competing interests. Funding Information: A.G.L. was supported by NIH (T32 HD091058, P2C HD050924, and P30 AG066615). A.G.T. was supported by NIH (T32HL007055). A.R.L. has been supported by the Leverhulme Trust (F/07 134/DF), the Excellence Initiative of Aix-Marseille University - A?MIDEX (a French ?Investissements d'Avenir? programme), the National Natural Science Foundation of China (#31771393), the Scientific and Technology Committee of Shanghai Municipality (18490750300), Ministry of Science and Technology of China (2020YFE0201600), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the 111 Project (B13016), and BBSRC (BB/I021213/1). L.F. was supported by NIH (R01CA204797). L.F.-R. was supported by an American Heart Association predoctoral grant (13PRE16100015). M.G. K.L.Y. and K.E.N. were supported by AHA (13GRNT16490017, 15GRNT25880008), R01DK089256, and R01DK101855. L.F.-R. C.A.H. and R.F.J.L. were supported by NIH (R01DK101855). X.R.G. was supported by NIH (R01EY022651). K.E.N. was supported by NIH (R01HD057194, R01DK122503, R01HG010297, R01HL142302, R01HL143885, and R01HG009974). L.G. was supported by NIH (T32 HL129982). Q.Q. was supported by NIH (R01HL060712, R01HL140976, and R01DK119268). S.F.A.G. was supported by the Daniel B. Burke Endowed Chair for Diabetes Research and NIH (R01 HD056465). X.G. M.A.A. Y.-D.I.C. J.Y. and J.I.R. were supported by NIH (EY14684, HL-0767711, HL-0697974, HL-088457, NEI EY11753, UL1-TR-001881). X.L. and K.R. were supported by NIH (R01 HL0767711 and DK-079888). Z.A. T.A.B. J.T. and A.H.X. were supported by HTN-IR funding (HL-0697974) and P.M.G. Y.H. E.I. and K.D.T. were supported by NIH (EY-14684). M.O.G. W.H. K.L. and K.S. were supported by NIH (HL-088457). A.E.J. was supported by NIH (K99/R00 HL130580). E.M.J. was supported by NIH (R01 CA063446, R01 CA077305, DOD RP9590546, and CBCRP 7PB-0068). J.M. was supported by the American Diabetes Association 1-19-ICTS-068 and by U01HG011723. C.W.K.C. was supported by R35GM142783. Study-specific acknowledgments are available as supplemental data. S.M.G. and A.M.S. receive funding from Seven Bridges Genomics to develop tools for the NHLBI BioData Catalyst consortium. All others authors declare no competing interests. Funding Information: A.G.L. was supported by NIH ( T32 HD091058 , P2C HD050924 , and P30 AG066615 ). A.G.T. was supported by NIH ( T32HL007055 ). A.R.L. has been supported by the Leverhulme Trust ( F/07 134/DF ), the Excellence Initiative of Aix-Marseille University - A∗MIDEX (a French “Investissements d’Avenir” programme), the National Natural Science Foundation of China ( #31771393 ), the Scientific and Technology Committee of Shanghai Municipality ( 18490750300 ), Ministry of Science and Technology of China ( 2020YFE0201600 ), Shanghai Municipal Science and Technology Major Project ( 2017SHZDZX01 ), the 111 Project ( B13016 ), and BBSRC ( BB/I021213/1 ). L.F. was supported by NIH ( R01CA204797 ). L.F.-R. was supported by an American Heart Association predoctoral grant ( 13PRE16100015 ). M.G., K.L.Y., and K.E.N. were supported by AHA ( 13GRNT16490017 , 15GRNT25880008 ), R01DK089256 , and R01DK101855 . L.F.-R., C.A.H., and R.F.J.L. were supported by NIH ( R01DK101855 ). X.R.G. was supported by NIH ( R01EY022651 ). K.E.N. was supported by NIH ( R01HD057194 , R01DK122503 , R01HG010297 , R01HL142302 , R01HL143885 , and R01HG009974 ). L.G. was supported by NIH ( T32 HL129982 ). Q.Q. was supported by NIH ( R01HL060712 , R01HL140976 , and R01DK119268 ). S.F.A.G. was supported by the Daniel B. Burke Endowed Chair for Diabetes Research and NIH ( R01 HD056465 ). X.G., M.A.A., Y.-D.I.C., J.Y., and J.I.R. were supported by NIH ( EY14684 , HL-0767711 , HL-0697974 , HL-088457 , NEI EY11753 , UL1-TR-001881 ). X.L. and K.R. were supported by NIH ( R01 HL0767711 and DK-079888 ). Z.A., T.A.B., J.T., and A.H.X. were supported by HTN-IR funding ( HL-0697974 ) and P.M.G., Y.H., E.I., and K.D.T. were supported by NIH ( EY-14684 ). M.O.G., W.H., K.L., and K.S. were supported by NIH ( HL-088457 ). A.E.J. was supported by NIH ( K99/R00 HL130580 ). E.M.J. was supported by NIH ( R01 CA063446 , R01 CA077305 , DOD RP9590546 , and CBCRP 7PB-0068 ). J.M. was supported by the American Diabetes Association 1-19-ICTS-068 and by U01HG011723 . C.W.K.C. was supported by R35GM142783 . Study-specific acknowledgments are available as supplemental data . Publisher Copyright: © 2022 The Author(s)

PY - 2022/4/14

Y1 - 2022/4/14

N2 - Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

AB - Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

KW - Hispanic/Latino

KW - anthropometrics

KW - diversity

KW - fine-mapping

KW - obesity

KW - population stratification

KW - trans-ancestral or trans-ethnic

UR - http://www.scopus.com/inward/record.url?scp=85127345671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85127345671&partnerID=8YFLogxK

U2 - 10.1016/j.xhgg.2022.100099

DO - 10.1016/j.xhgg.2022.100099

M3 - Article

C2 - 35399580

AN - SCOPUS:85127345671

SN - 2666-2477

VL - 3

JO - Human Genetics and Genomics Advances

JF - Human Genetics and Genomics Advances

IS - 2

M1 - 100099

ER -

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium

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