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.
| Original language | English |
|---|---|
| Article number | 100099 |
| Journal | Human Genetics and Genomics Advances |
| Volume | 3 |
| Issue number | 2 |
| Number of pages | 21 |
| DOIs | |
| Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:© 2022 The Author(s)
Keywords
- anthropometrics
- diversity
- fine-mapping
- Hispanic/Latino
- obesity
- population stratification
- trans-ancestral or trans-ethnic
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Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium. / Fernández-Rhodes, Lindsay; Graff, Mariaelisa; Buchanan, Victoria L.; Justice, Anne E.; Highland, Heather M.; Guo, Xiuqing; Zhu, Wanying; Chen, Hung Hsin; Young, Kristin L.; Adhikari, Kaustubh; Palmer, Nicholette D.; Below, Jennifer E.; Bradfield, Jonathan; Pereira, Alexandre C.; Glover, LáShauntá S.; Kim, Daeeun; Lilly, Adam G.; Shrestha, Poojan; Thomas, Alvin G.; Zhang, Xinruo; Chen, Minhui; Chiang, Charleston W.K.; Pulit, Sara; Horimoto, Andrea; Krieger, Jose E.; Guindo-Martínez, Marta; Preuss, Michael; Schumann, Claudia; Smit, Roelof A.J.; Torres-Mejía, Gabriela; Acuña-Alonzo, Victor; Bedoya, Gabriel; Bortolini, Maria Cátira; Canizales-Quinteros, Samuel; Gallo, Carla; González-José, Rolando; Poletti, Giovanni; Rothhammer, Francisco; Hakonarson, Hakon; Igo, Robert; Adler, Sharon G.; Iyengar, Sudha K.; Nicholas, Susanne B.; Gogarten, Stephanie M.; Isasi, Carmen R.; Papnicolaou, George; Stilp, Adrienne M.; Qi, Qibin; Kho, Minjung; Smith, Jennifer A.; Langefeld, Carl D.; Wagenknecht, Lynne; Mckean-Cowdin, Roberta; Gao, Xiaoyi Raymond; Nousome, Darryl; Conti, David V.; Feng, Ye; Allison, Matthew A.; Arzumanyan, Zorayr; Buchanan, Thomas A.; Ida Chen, Yii Der; Genter, Pauline M.; Goodarzi, Mark O.; Hai, Yang; Hsueh, Willa; Ipp, Eli; Kandeel, Fouad R.; Lam, Kelvin; Li, Xiaohui; Nadler, Jerry L.; Raffel, Leslie J.; Roll, Kathryn; Sandow, Kevin; Tan, Jingyi; Taylor, Kent D.; Xiang, Anny H.; Yao, Jie; Audirac-Chalifour, Astride; de Jesus Peralta Romero, Jose; Hartwig, Fernando; Horta, Bernando; Blangero, John; Curran, Joanne E.; Duggirala, Ravindranath; Lehman, Donna E.; Puppala, Sobha; Fejerman, Laura; John, Esther M.; Aguilar-Salinas, Carlos; Burtt, Noël P.; Florez, Jose C.; García-Ortíz, Humberto; González-Villalpando, Clicerio; Mercader, Josep; Orozco, Lorena; Tusié-Luna, Teresa; Blanco, Estela; Gahagan, Sheila; Cox, Nancy J.; Hanis, Craig; Butte, Nancy F.; Cole, Shelley A.; Comuzzie, Anthony G.; Voruganti, V. Saroja; Rohde, Rebecca; Wang, Yujie; Sofer, Tamar; Ziv, Elad; Grant, Struan F.A.; Ruiz-Linares, Andres; Rotter, Jerome I.; Haiman, Christopher A.; Parra, Esteban J.; Cruz, Miguel; Loos, Ruth J.F.; North, Kari E.
In: Human Genetics and Genomics Advances, Vol. 3, No. 2, 100099, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
}
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 - Publisher Copyright: © 2022 The Author(s)
PY - 2022
Y1 - 2022
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 - anthropometrics
KW - diversity
KW - fine-mapping
KW - Hispanic/Latino
KW - obesity
KW - population stratification
KW - trans-ancestral or trans-ethnic
U2 - 10.1016/j.xhgg.2022.100099
DO - 10.1016/j.xhgg.2022.100099
M3 - Journal article
C2 - 35399580
AN - SCOPUS:85127345671
VL - 3
JO - Human Genetics and Genomics Advances
JF - Human Genetics and Genomics Advances
SN - 2666-2477
IS - 2
M1 - 100099
ER -