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Start Over Author "Chiang, Charleston WK" Journal human genetics and genomics advances
3 results on '"Chiang, Charleston WK"'

1. Evaluating genomic polygenic risk scores for childhood acute lymphoblastic leukemia in Latinos

Author

Jeon, Soyoung, Lo, Ying Chu, Morimoto, Libby M, Metayer, Catherine, Ma, Xiaomei, Wiemels, Joseph L, de Smith, Adam J, and Chiang, Charleston WK

Subjects
Biological Sciences, Genetics, Hematology, Pediatric Cancer, Pediatric, Cancer, Rare Diseases, Childhood Leukemia, Human Genome, Humans, Genetic Predisposition to Disease, Genomics, Child, United States, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Genome-Wide Association Study, Hispanic or Latino, Genetic Risk Score, acute lymphoblastic leukemia, latinos, polygenic risk scores, risk prediction
Abstract

The utility of polygenic risk score (PRS) models has not been comprehensively evaluated for childhood acute lymphoblastic leukemia (ALL), the most common type of cancer in children. Previous PRS models for ALL were based on significant loci observed in genome-wide association studies (GWASs), even though genomic PRS models have been shown to improve prediction performance for a number of complex diseases. In the United States, Latino (LAT) children have the highest risk of ALL, but the transferability of PRS models to LAT children has not been studied. In this study, we constructed and evaluated genomic PRS models based on either non-Latino White (NLW) GWAS or a multi-ancestry GWAS. We found that the best PRS models performed similarly between held-out NLW and LAT samples (PseudoR2 = 0.086 ± 0.023 in NLW vs. 0.060 ± 0.020 in LAT), and can be improved for LAT if we performed GWAS in LAT-only (PseudoR2 = 0.116 ± 0.026) or multi-ancestry samples (PseudoR2 = 0.131 ± 0.025). However, the best genomic models currently do not have better prediction accuracy than a conventional model using all known ALL-associated loci in the literature (PseudoR2 = 0.166 ± 0.025), which includes loci from GWAS populations that we could not access to train genomic PRS models. Our results suggest that larger and more inclusive GWASs may be needed for genomic PRS to be useful for ALL. Moreover, the comparable performance between populations may suggest a more oligogenic architecture for ALL, where some large effect loci may be shared between populations. Future PRS models that move away from the infinite causal loci assumption may further improve PRS for ALL.

Published
2023

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

Author

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, Kim, Daeeun, Lilly, Adam G, Shrestha, Poojan, Thomas, Alvin G, Zhang, Xinruo, Chen, Minhui, Chiang, Charleston WK, Pulit, Sara, Horimoto, Andrea, Krieger, Jose E, Guindo-Martínez, Marta, Preuss, Michael, Schumann, Claudia, Smit, Roelof AJ, 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, Chen, Yii-Der Ida, 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, Peralta Romero, Jose de Jesus, 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, and Hanis, Craig

Abstract

[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].

Published
2023

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

Author

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, Kim, Daeeun, Lilly, Adam G, Shrestha, Poojan, Thomas, Alvin G, Zhang, Xinruo, Chen, Minhui, Chiang, Charleston WK, Pulit, Sara, Horimoto, Andrea, Krieger, Jose E, Guindo-Martínez, Marta, Preuss, Michael, Schumann, Claudia, Smit, Roelof AJ, 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, Chen, Yii-Der Ida, 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, and Hanis, Craig

Subjects
Biological Sciences, Genetics, Obesity, Human Genome, Hispanic/Latino, anthropometrics, diversity, fine-mapping, obesity, population stratification, trans-ancestral or trans-ethnic
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.

Published
2022

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