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Cited by 513

The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.

Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data

Open access
Wainschtein, Pierrick, Jain, Deepti, Zheng, Zhili, TOPMed Anthropometry Working Group, Aslibekyan, Stella, Becker, Diane, Bi, Wenjian, Brody, Jennifer, Carlson, Jenna C., Correa, Adolfo, Du, Margaret Mengmeng, Fernandez-Rhodes, Lindsay, Ferrier, Kendra R., Graff, Misa, Guo, Xiuqing, He, Jiang, Heard-Costa, Nancy L., Highland, Heather M., Hirschhorn, Joel N., Howard-Claudio, Candace M., Isasi, Carmen R., Jackson, Rebecca, Jiang, Jicai, Joehanes, Roby, Justice, Anne E., Kalyani, Rita R., Kardia, Sharon, Lange, Ethan, LeBoff, Meryl, Lee, Seunggeun, Li, Xihao, Li, Zilin, Lim, Elise, Lin, Danyu, Lin, Xihong, Liu, Simin, Lu, Yingchang, Manson, JoAnn, Martin, Lisa, McHugh, Caitlin, Mikulla, Julie, Musani, Solomon K., Ng, Maggie, Nickerson, Deborah, Palmer, Nicholette, Perry, James, Peters, Ulrike, Preuss, Michael, Qi, Qibin, Raffield, Laura, Rasmussen-Torvik, Laura, Reiner, Alex, Russell, Emily M., Sitlani, Colleen, Smith, Jennifer, Spracklen, Cassandra N., Wang, Tao, Wang, Zhe, Wessel, Jennifer, Xu, Hanfei, Yaser, Mohammad, Yoneyama, Sachiko, Young, Kendra A., Zhang, Jingwen, Zhang, Xinruo, Zhou, Hufeng, Zhu, Xiaofeng, Zoellner, Sebastian, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Ashley-Koch, Allison, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Bowden, Donald W., Bowler, Russell, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April, Carty, Cara, Casaburi, Richard, Romero, Juan P. Casas, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Crandall, Carolyn, Crapo, James, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Gupta, Namrata, Haas, David M., Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., Heavner, Ben, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao Agnes, Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kramer, Holly, Lange, Christoph, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Liu, Yongmei, Liu, Yu, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Marton, Melissa, Mathai, Susan, May, Susanne, McArdle, Patrick, McFarland, Sean, McGoldrick, Daniel, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A., Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nkechinyere, Osuji, O’Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Peyser, Patricia, Phillips, Lawrence S., Pleiness, Jacob, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Rajendran, Mahitha, Rao, D. C., Ratan, Aakrosh, Reed, Robert, Reeves, Catherine, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Robillard, Rebecca, Robine, Nicolas, Roselli, Carolina, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Josh, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent D., Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weiss, Scott T., Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Joseph, Xu, Huichun, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zody, Michael, Cupples, L. Adrienne, Shadyab, Aladdin H., McKnight, Barbara, Shoemaker, Benjamin M., Mitchell, Braxton D., Psaty, Bruce M., Kooperberg, Charles, Liu, Ching-Ti, Albert, Christine M., Roden, Dan, Chasman, Daniel I., Darbar, Dawood, Lloyd-Jones, Donald M., Arnett, Donna K., Regan, Elizabeth A., Boerwinkle, Eric, Rotter, Jerome I., O’Connell, Jeffrey R., Yanek, Lisa R., de Andrade, Mariza, Allison, Matthew A., McDonald, Merry-Lynn N., Chung, Mina K., Fornage, Myriam, Chami, Nathalie, Smith, Nicholas L., Ellinor, Patrick T., Vasan, Ramachandran S., Mathias, Rasika A., Loos, Ruth J. F., Rich, Stephen S., Lubitz, Steven A., Heckbert, Susan R., Redline, Susan, Guo, Xiuqing, Chen, Y. -D Ida, Laurie, Cecelia A., Hernandez, Ryan D., McGarvey, Stephen T., Goddard, Michael E., Laurie, Cathy C., North, Kari E., Lange, Leslie A., Weir, Bruce S., Yengo, Loic, Yang, Jian, Visscher, Peter M.·2022·Nature Genetics
DOI 10.1038/s41588-021-00997-7

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Abstract

Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular whether the causal variants are rare, or whether it is overestimated due to bias in inference from pedigree data. Here we estimated heritability for height and body mass index (BMI) from whole-genome sequence data on 25,465 unrelated individuals of European ancestry. The estimated heritability was 0.68 (standard error 0.10) for height and 0.30 (standard error 0.10) for body mass index. Low minor allele frequency variants in low linkage disequilibrium (LD) with neighboring variants were enriched for heritability, to a greater extent for protein-altering variants, consistent with negative selection. Our results imply that rare variants, in particular those in regions of low linkage disequilibrium, are a major source of the still missing heritability of complex traits and disease. Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

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Authors
Wainschtein, P., Jain, D., Zheng, Z., TOPMed Anthropometry Working Group, Aslibekyan, S., Becker, D., Bi, W., Brody, J., Carlson, J. C., Correa, A., Du, M. M., Fernandez-Rhodes, L., Ferrier, K. R., Graff, M., Guo, X., He, J., Heard-Costa, N. L., Highland, H. M., Hirschhorn, J. N., Howard-Claudio, C. M., Isasi, C. R., Jackson, R., Jiang, J., Joehanes, R., Justice, A. E., Kalyani, R. R., Kardia, S., Lange, E., LeBoff, M., Lee, S., Li, X., Li, Z., Lim, E., Lin, D., Lin, X., Liu, S., Lu, Y., Manson, J., Martin, L., McHugh, C., Mikulla, J., Musani, S. K., Ng, M., Nickerson, D., Palmer, N., Perry, J., Peters, U., Preuss, M., Qi, Q., Raffield, L., Rasmussen-Torvik, L., Reiner, A., Russell, E. M., Sitlani, C., Smith, J., Spracklen, C. N., Wang, T., Wang, Z., Wessel, J., Xu, H., Yaser, M., Yoneyama, S., Young, K. A., Zhang, J., Zhang, X., Zhou, H., Zhu, X., Zoellner, S., NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Abe, N., Abecasis, G., Aguet, F., Almasy, L., Alonso, A., Ament, S., Anderson, P., Anugu, P., Applebaum-Bowden, D., Ardlie, K., Arking, D., Ashley-Koch, A., Assimes, T., Auer, P., Avramopoulos, D., Ayas, N., Balasubramanian, A., Barnard, J., Barnes, K., Barr, R. G., Barron-Casella, E., Barwick, L., Beaty, T., Beck, G., Becker, L., Beer, R., Beitelshees, A., Benjamin, E., Benos, T., Bezerra, M., Bielak, L., Bis, J., Blackwell, T., Blangero, J., Bowden, D. W., Bowler, R., Broeckel, U., Broome, J., Brown, D., Bunting, K., Burchard, E., Bustamante, C., Buth, E., Cade, B., Cardwell, J., Carey, V., Carrier, J., Carson, A., Carty, C., Casaburi, R., Romero, J. P. C., Casella, J., Castaldi, P., Chaffin, M., Chang, C., Chang, Y.-C., Chavan, S., Chen, B.-J., Chen, W.-M., Cho, M., Choi, S. H., Chuang, L.-M., Chung, R.-H., Clish, C., Comhair, S., Conomos, M., Cornell, E., Crandall, C., Crapo, J., Curran, J., Curtis, J., Custer, B., Damcott, C., Darbar, D., David, S., Davis, C., Daya, M., de las Fuentes, L., de Vries, P., DeBaun, M., Deka, R., DeMeo, D., Devine, S., Dinh, H., Doddapaneni, H., Duan, Q., Dugan-Perez, S., Duggirala, R., Durda, J. P., Dutcher, S. K., Eaton, C., Ekunwe, L., El Boueiz, A., Emery, L., Erzurum, S., Farber, C., Farek, J., Fingerlin, T., Flickinger, M., Franceschini, N., Frazar, C., Fu, M., Fullerton, S. M., Fulton, L., Gabriel, S., Gan, W., Gao, S., Gao, Y., Gass, M., Geiger, H., Gelb, B., Geraci, M., Germer, S., Gerszten, R., Ghosh, A., Gibbs, R., Gignoux, C., Gladwin, M., Glahn, D., Gogarten, S., Gong, D.-W., Goring, H., Graw, S., Gray, K. J., Grine, D., Gross, C., Gu, C. C., Guan, Y., Gupta, N., Haas, D. M., Haessler, J., Hall, M., Han, Y., Hanly, P., Harris, D., Hawley, N. L., Heavner, B., Herrington, D., Hersh, C., Hidalgo, B., Hixson, J., Hobbs, B., Hokanson, J., Hong, E., Hoth, K., Hsiung, C. A., Hu, J., Hung, Y.-J., Huston, H., Hwu, C. M., Irvin, M. R., Jaquish, C., Johnsen, J., Johnson, A., Johnson, C., Johnston, R., Jones, K., Kang, H. M., Kaplan, R., Kelly, S., Kenny, E., Kessler, M., Khan, A., Khan, Z., Kim, W., Kimoff, J., Kinney, G., Konkle, B., Kramer, H., Lange, C., Lee, J., Lee, S., Lee, W.-J., LeFaive, J., Levine, D., Levy, D., Lewis, J., Li, X., Li, Y., Lin, H., Lin, H., Liu, Y., Liu, Y., Lunetta, K., Luo, J., Magalang, U., Mahaney, M., Make, B., Manichaikul, A., Manning, A., Marton, M., Mathai, S., May, S., McArdle, P., McFarland, S., McGoldrick, D., McNeil, B., Mei, H., Meigs, J., Menon, V., Mestroni, L., Metcalf, G., Meyers, D. A., Mignot, E., Mikulla, J., Min, N., Minear, M., Minster, R. L., Moll, M., Momin, Z., Montasser, M. E., Montgomery, C., Muzny, D., Mychaleckyj, J. C., Nadkarni, G., Naik, R., Naseri, T., Natarajan, P., Nekhai, S., Nelson, S. C., Neltner, B., Nessner, C., Nkechinyere, O., O’Connor, T., Ochs-Balcom, H., Okwuonu, G., Pack, A., Paik, D. T., Palmer, N., Pankow, J., Papanicolaou, G., Parker, C., Peloso, G., Peralta, J. M., Perez, M., Peyser, P., Phillips, L. S., Pleiness, J., Pollin, T., Post, W., Becker, J. P., Boorgula, M. P., Qasba, P., Qiao, D., Qin, Z., Rafaels, N., Rajendran, M., Rao, D. C., Ratan, A., Reed, R., Reeves, C., Reupena, M. S., Rice, K., Robillard, R., Robine, N., Roselli, C., Ruczinski, I., Runnels, A., Russell, P., Ruuska, S., Ryan, K., Sabino, E. C., Saleheen, D., Salimi, S., Salvi, S., Salzberg, S., Sandow, K., Sankaran, V. G., Santibanez, J., Schwander, K., Schwartz, D., Sciurba, F., Seidman, C., Seidman, J., Sheehan, V., Sherman, S. L., Shetty, A., Shetty, A., Sheu, W. H.-H., Silver, B., Silverman, E., Skomro, R., Smith, A. V., Smith, J., Smith, T., Smoller, S., Snively, B., Snyder, M., Sofer, T., Sotoodehnia, N., Stilp, A. M., Storm, G., Streeten, E., Su, J. L., Sung, Y. J., Sylvia, J., Szpiro, A., Taliun, D., Tang, H., Taub, M., Taylor, K. D., Taylor, M., Taylor, S., Telen, M., Thornton, T. A., Threlkeld, M., Tinker, L., Tirschwell, D., Tishkoff, S., Tiwari, H., Tong, C., Tracy, R., Tsai, M., Vaidya, D., Van Den Berg, D., VandeHaar, P., Vrieze, S., Walker, T., Wallace, R., Walts, A., Wang, F. F., Wang, H., Wang, J., Watson, K., Watt, J., Weeks, D. E., Weinstock, J., Weiss, S. T., Weng, L.-C., Willer, C., Williams, K., Williams, L. K., Wilson, C., Wilson, J., Winterkorn, L., Wong, Q., Wu, J., Xu, H., Yang, I., Yu, K., Zekavat, S. M., Zhang, Y., Zhao, S. X., Zhao, W., Zody, M., Cupples, L. A., Shadyab, A. H., McKnight, B., Shoemaker, B. M., Mitchell, B. D., Psaty, B. M., Kooperberg, C., Liu, C.-T., Albert, C. M., Roden, D., Chasman, D. I., Darbar, D., Lloyd-Jones, D. M., Arnett, D. K., Regan, E. A., Boerwinkle, E., Rotter, J. I., O’Connell, J. R., Yanek, L. R., de Andrade, M., Allison, M. A., McDonald, M.-L. N., Chung, M. K., Fornage, M., Chami, N., Smith, N. L., Ellinor, P. T., Vasan, R. S., Mathias, R. A., Loos, R. J. F., Rich, S. S., Lubitz, S. A., Heckbert, S. R., Redline, S., Guo, X., Chen, Y. D. I., Laurie, C. A., Hernandez, R. D., McGarvey, S. T., Goddard, M. E., Laurie, C. C., North, K. E., Lange, L. A., Weir, B. S., Yengo, L., Yang, J., & Visscher, P. M.
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2022-03
Volume
54
Issue
3
Pages
263-273
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/s41588-021-00997-7
OpenAlex
W4220827000
Cited by
513
References
53
FWCI
43.21
Type
journal article
Language
en
Open access
green

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Wainschtein, P., Jain, D., Zheng, Z., TOPMed Anthropometry Working Group, Aslibekyan, S., Becker, D., Bi, W., Brody, J., Carlson, J. C., Correa, A., Du, M. M., Fernandez-Rhodes, L., Ferrier, K. R., Graff, M., Guo, X., He, J., Heard-Costa, N. L., Highland, H. M., Hirschhorn, J. N., . . . Visscher, P. M. (2022). Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data. Nature Genetics. https://doi.org/10.1038/s41588-021-00997-7

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