A nondegenerate code of deleterious variants in mendelian Loci contributes to complex disease risk

Research output: Contribution to journalJournal articlepeer-review

Standard

A nondegenerate code of deleterious variants in mendelian Loci contributes to complex disease risk. / Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey.

In: Cell, Vol. 155, No. 1, 26.09.2013, p. 70-80.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Blair, DR, Lyttle, CS, Mortensen, JM, Bearden, CF, Jensen, AB, Khiabanian, H, Melamed, R, Rabadan, R, Bernstam, EV, Brunak, S, Jensen, LJ, Nicolae, D, Shah, NH, Grossman, RL, Cox, NJ, White, KP & Rzhetsky, A 2013, 'A nondegenerate code of deleterious variants in mendelian Loci contributes to complex disease risk', Cell, vol. 155, no. 1, pp. 70-80. https://doi.org/10.1016/j.cell.2013.08.030

APA

Blair, D. R., Lyttle, C. S., Mortensen, J. M., Bearden, C. F., Jensen, A. B., Khiabanian, H., Melamed, R., Rabadan, R., Bernstam, E. V., Brunak, S., Jensen, L. J., Nicolae, D., Shah, N. H., Grossman, R. L., Cox, N. J., White, K. P., & Rzhetsky, A. (2013). A nondegenerate code of deleterious variants in mendelian Loci contributes to complex disease risk. Cell, 155(1), 70-80. https://doi.org/10.1016/j.cell.2013.08.030

Vancouver

Blair DR, Lyttle CS, Mortensen JM, Bearden CF, Jensen AB, Khiabanian H et al. A nondegenerate code of deleterious variants in mendelian Loci contributes to complex disease risk. Cell. 2013 Sep 26;155(1):70-80. https://doi.org/10.1016/j.cell.2013.08.030

Author

Blair, David R ; Lyttle, Christopher S ; Mortensen, Jonathan M ; Bearden, Charles F ; Jensen, Anders Boeck ; Khiabanian, Hossein ; Melamed, Rachel ; Rabadan, Raul ; Bernstam, Elmer V ; Brunak, Søren ; Jensen, Lars Juhl ; Nicolae, Dan ; Shah, Nigam H ; Grossman, Robert L ; Cox, Nancy J ; White, Kevin P ; Rzhetsky, Andrey. / A nondegenerate code of deleterious variants in mendelian Loci contributes to complex disease risk. In: Cell. 2013 ; Vol. 155, No. 1. pp. 70-80.

Bibtex

@article{ffa34e55f9b4484da76881ead13c1c61,
title = "A nondegenerate code of deleterious variants in mendelian Loci contributes to complex disease risk",
abstract = "Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this {"}Mendelian code.{"} Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases.",
author = "Blair, {David R} and Lyttle, {Christopher S} and Mortensen, {Jonathan M} and Bearden, {Charles F} and Jensen, {Anders Boeck} and Hossein Khiabanian and Rachel Melamed and Raul Rabadan and Bernstam, {Elmer V} and S{\o}ren Brunak and Jensen, {Lars Juhl} and Dan Nicolae and Shah, {Nigam H} and Grossman, {Robert L} and Cox, {Nancy J} and White, {Kevin P} and Andrey Rzhetsky",
note = "Copyright {\textcopyright} 2013 Elsevier Inc. All rights reserved.",
year = "2013",
month = sep,
day = "26",
doi = "10.1016/j.cell.2013.08.030",
language = "English",
volume = "155",
pages = "70--80",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - A nondegenerate code of deleterious variants in mendelian Loci contributes to complex disease risk

AU - Blair, David R

AU - Lyttle, Christopher S

AU - Mortensen, Jonathan M

AU - Bearden, Charles F

AU - Jensen, Anders Boeck

AU - Khiabanian, Hossein

AU - Melamed, Rachel

AU - Rabadan, Raul

AU - Bernstam, Elmer V

AU - Brunak, Søren

AU - Jensen, Lars Juhl

AU - Nicolae, Dan

AU - Shah, Nigam H

AU - Grossman, Robert L

AU - Cox, Nancy J

AU - White, Kevin P

AU - Rzhetsky, Andrey

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/9/26

Y1 - 2013/9/26

N2 - Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases.

AB - Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases.

U2 - 10.1016/j.cell.2013.08.030

DO - 10.1016/j.cell.2013.08.030

M3 - Journal article

C2 - 24074861

VL - 155

SP - 70

EP - 80

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -

ID: 57409995