Common DNA Variants Accurately Rank an Individual of Extreme Height

Corinne E. Sexton; Mark T.W. Ebbert; Ryan H. Miller; Meganne Ferrel; Jo Ann T. Tschanz; Christopher D. Corcoran; Perry G. Ridge; John S.K. Kauwe

doi:10.1155/2018/5121540

Common DNA Variants Accurately Rank an Individual of Extreme Height

Corinne E. Sexton, Mark T.W. Ebbert, Ryan H. Miller, Meganne Ferrel, Jo Ann T. Tschanz, Christopher D. Corcoran, Perry G. Ridge, John S.K. Kauwe

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

4 Scopus citations

Abstract

Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7′6″, 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals.

Original language	English
Article number	5121540
Journal	International Journal of Genomics
Volume	2018
DOIs	https://doi.org/10.1155/2018/5121540
State	Published - 2018

Bibliographical note

Funding Information:
The authors thank Mr. Bradley and the participants and staff of the centers that were involved in the data collection for ADNI and the Cache County study for their important contributions to this work. The data used in the preparation of this article were obtained in part from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http://adni. loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/ uploads/how-to-apply/ADNI-Acknowledgement-List.pdf. Whole-genome data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI), National Institutes of Health Grant (U01 AG024904), and DOD ADNI, Department of Defense award (W81XWH-12-2-001). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern Rev December 5, 2013 California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California.

Funding Information:
The authors thank Mr. Bradley and the participants and staff of the centers that were involved in the data collection for ADNI and the Cache County study for their important contributions to this work. The data used in the preparation of this article were obtained in part from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni. loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/ uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. Whole-genome data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), National Institutes of Health Grant (U01 AG024904), and DOD ADNI, Department of Defense award (W81XWH-12-2-001). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern Rev December 5, 2013 California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California.

Publisher Copyright:
© 2018 Corinne E. Sexton et al.

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics
Pharmaceutical Science

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10.1155/2018/5121540

Cite this

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title = "Common DNA Variants Accurately Rank an Individual of Extreme Height",

abstract = "Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7′6″, 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals.",

author = "Sexton, {Corinne E.} and Ebbert, {Mark T.W.} and Miller, {Ryan H.} and Meganne Ferrel and Tschanz, {Jo Ann T.} and Corcoran, {Christopher D.} and Ridge, {Perry G.} and Kauwe, {John S.K.}",

note = "Funding Information: The authors thank Mr. Bradley and the participants and staff of the centers that were involved in the data collection for ADNI and the Cache County study for their important contributions to this work. The data used in the preparation of this article were obtained in part from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http://adni. loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/ uploads/how-to-apply/ADNI-Acknowledgement-List.pdf. Whole-genome data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI), National Institutes of Health Grant (U01 AG024904), and DOD ADNI, Department of Defense award (W81XWH-12-2-001). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern Rev December 5, 2013 California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California. Funding Information: The authors thank Mr. Bradley and the participants and staff of the centers that were involved in the data collection for ADNI and the Cache County study for their important contributions to this work. The data used in the preparation of this article were obtained in part from the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) database (http://adni. loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/ uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. Whole-genome data collection and sharing for this project was funded by the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI), National Institutes of Health Grant (U01 AG024904), and DOD ADNI, Department of Defense award (W81XWH-12-2-001). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer{\textquoteright}s Association; Alzheimer{\textquoteright}s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern Rev December 5, 2013 California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2018 Corinne E. Sexton et al.",

year = "2018",

doi = "10.1155/2018/5121540",

language = "English",

volume = "2018",

}

TY - JOUR

T1 - Common DNA Variants Accurately Rank an Individual of Extreme Height

AU - Sexton, Corinne E.

AU - Ebbert, Mark T.W.

AU - Miller, Ryan H.

AU - Ferrel, Meganne

AU - Tschanz, Jo Ann T.

AU - Corcoran, Christopher D.

AU - Ridge, Perry G.

AU - Kauwe, John S.K.

N1 - Funding Information: The authors thank Mr. Bradley and the participants and staff of the centers that were involved in the data collection for ADNI and the Cache County study for their important contributions to this work. The data used in the preparation of this article were obtained in part from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http://adni. loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/ uploads/how-to-apply/ADNI-Acknowledgement-List.pdf. Whole-genome data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI), National Institutes of Health Grant (U01 AG024904), and DOD ADNI, Department of Defense award (W81XWH-12-2-001). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern Rev December 5, 2013 California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California. Funding Information: The authors thank Mr. Bradley and the participants and staff of the centers that were involved in the data collection for ADNI and the Cache County study for their important contributions to this work. The data used in the preparation of this article were obtained in part from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni. loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/ uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. Whole-genome data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), National Institutes of Health Grant (U01 AG024904), and DOD ADNI, Department of Defense award (W81XWH-12-2-001). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern Rev December 5, 2013 California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California. Publisher Copyright: © 2018 Corinne E. Sexton et al.

PY - 2018

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N2 - Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7′6″, 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals.

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Common DNA Variants Accurately Rank an Individual of Extreme Height

Abstract

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