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Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum. / Ganna, Andrea; Satterstrom, F. Kyle; Zekavat, Seyedeh M.; Das, Indraniel; Kurki, Mitja I.; Churchhouse, Claire; Alfoldi, Jessica; Martin, Alicia R.; Havulinna, Aki S.; Byrnes, Andrea; Thompson, Wesley K.; Nielsen, Philip R.; Karczewski, Konrad J.; Saarentaus, Elmo; Rivas, Manuel A.; Gupta, Namrata; Pietiläinen, Olli; Emdin, Connor A.; Lescai, Francesco; Bybjerg-Grauholm, Jonas; Flannick, Jason; GoT2D/T2D-GENES Consortium; Mercader, Josep M.; Udler, Miriam; SIGMA Consortium Helmsley IBD Exome Sequencing Project; FinMetSeq Consortium; iPSYCH-Broad Consortium; Laakso, Markku; Salomaa, Veikko; Hultman, Christina; Ripatti, Samuli; Hämäläinen, Eija; Moilanen, Jukka S.; Körkkö, Jarmo; Kuismin, Outi; Nordentoft, Merete; Hougaard, David M.; Mors, Ole; Werge, Thomas; Mortensen, Preben Bo; MacArthur, Daniel; Daly, Mark J.; Sullivan, Patrick F.; Locke, Adam E.; Palotie, Aarno; Børglum, Anders D.; Kathiresan, Sekar; Neale, Benjamin M.
I:
American Journal of Human Genetics, Bind 102, Nr. 6, 2018, s. 1204-1211.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
Ganna, A, Satterstrom, FK, Zekavat, SM, Das, I, Kurki, MI, Churchhouse, C, Alfoldi, J, Martin, AR, Havulinna, AS, Byrnes, A, Thompson, WK, Nielsen, PR, Karczewski, KJ, Saarentaus, E, Rivas, MA, Gupta, N, Pietiläinen, O, Emdin, CA, Lescai, F, Bybjerg-Grauholm, J, Flannick, J, GoT2D/T2D-GENES Consortium, Mercader, JM, Udler, M, SIGMA Consortium Helmsley IBD Exome Sequencing Project, FinMetSeq Consortium, iPSYCH-Broad Consortium, Laakso, M, Salomaa, V, Hultman, C, Ripatti, S, Hämäläinen, E, Moilanen, JS, Körkkö, J, Kuismin, O
, Nordentoft, M, Hougaard, DM, Mors, O
, Werge, T, Mortensen, PB, MacArthur, D, Daly, MJ, Sullivan, PF, Locke, AE, Palotie, A, Børglum, AD, Kathiresan, S & Neale, BM 2018, '
Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum',
American Journal of Human Genetics, bind 102, nr. 6, s. 1204-1211.
https://doi.org/10.1016/j.ajhg.2018.05.002APA
Ganna, A., Satterstrom, F. K., Zekavat, S. M., Das, I., Kurki, M. I., Churchhouse, C., Alfoldi, J., Martin, A. R., Havulinna, A. S., Byrnes, A., Thompson, W. K., Nielsen, P. R., Karczewski, K. J., Saarentaus, E., Rivas, M. A., Gupta, N., Pietiläinen, O., Emdin, C. A., Lescai, F., ... Neale, B. M. (2018).
Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum.
American Journal of Human Genetics,
102(6), 1204-1211.
https://doi.org/10.1016/j.ajhg.2018.05.002Vancouver
Ganna A, Satterstrom FK, Zekavat SM, Das I, Kurki MI, Churchhouse C o.a.
Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum.
American Journal of Human Genetics. 2018;102(6):1204-1211.
https://doi.org/10.1016/j.ajhg.2018.05.002Author
Ganna, Andrea ; Satterstrom, F. Kyle ; Zekavat, Seyedeh M. ; Das, Indraniel ; Kurki, Mitja I. ; Churchhouse, Claire ; Alfoldi, Jessica ; Martin, Alicia R. ; Havulinna, Aki S. ; Byrnes, Andrea ; Thompson, Wesley K. ; Nielsen, Philip R. ; Karczewski, Konrad J. ; Saarentaus, Elmo ; Rivas, Manuel A. ; Gupta, Namrata ; Pietiläinen, Olli ; Emdin, Connor A. ; Lescai, Francesco ; Bybjerg-Grauholm, Jonas ; Flannick, Jason ; GoT2D/T2D-GENES Consortium ; Mercader, Josep M. ; Udler, Miriam ; SIGMA Consortium Helmsley IBD Exome Sequencing Project ; FinMetSeq Consortium ; iPSYCH-Broad Consortium ; Laakso, Markku ; Salomaa, Veikko ; Hultman, Christina ; Ripatti, Samuli ; Hämäläinen, Eija ; Moilanen, Jukka S. ; Körkkö, Jarmo ; Kuismin, Outi ; Nordentoft, Merete ; Hougaard, David M. ; Mors, Ole ; Werge, Thomas ; Mortensen, Preben Bo ; MacArthur, Daniel ; Daly, Mark J. ; Sullivan, Patrick F. ; Locke, Adam E. ; Palotie, Aarno ; Børglum, Anders D. ; Kathiresan, Sekar ; Neale, Benjamin M. / Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum. I: American Journal of Human Genetics. 2018 ; Bind 102, Nr. 6. s. 1204-1211.
Bibtex
@article{714d72d8877b4be0af933524b5f0a93c,
title = "Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum",
abstract = "There is a limited understanding about the impact of rare protein-truncating variants across multiple phenotypes. We explore the impact of this class of variants on 13 quantitative traits and 10 diseases using whole-exome sequencing data from 100,296 individuals. Protein-truncating variants in genes intolerant to this class of mutations increased risk of autism, schizophrenia, bipolar disorder, intellectual disability, and ADHD. In individuals without these disorders, there was an association with shorter height, lower education, increased hospitalization, and reduced age at enrollment. Gene sets implicated from GWASs did not show a significant protein-truncating variants burden beyond what was captured by established Mendelian genes. In conclusion, we provide a thorough investigation of the impact of rare deleterious coding variants on complex traits, suggesting widespread pleiotropic risk.",
keywords = "burden analysis, constraint genes, exome sequencing, phewas, rare variants, selection, ultra-rare variants",
author = "Andrea Ganna and Satterstrom, {F. Kyle} and Zekavat, {Seyedeh M.} and Indraniel Das and Kurki, {Mitja I.} and Claire Churchhouse and Jessica Alfoldi and Martin, {Alicia R.} and Havulinna, {Aki S.} and Andrea Byrnes and Thompson, {Wesley K.} and Nielsen, {Philip R.} and Karczewski, {Konrad J.} and Elmo Saarentaus and Rivas, {Manuel A.} and Namrata Gupta and Olli Pietil{\"a}inen and Emdin, {Connor A.} and Francesco Lescai and Jonas Bybjerg-Grauholm and Jason Flannick and {GoT2D/T2D-GENES Consortium} and Mercader, {Josep M.} and Miriam Udler and {SIGMA Consortium Helmsley IBD Exome Sequencing Project} and {FinMetSeq Consortium} and {iPSYCH-Broad Consortium} and Markku Laakso and Veikko Salomaa and Christina Hultman and Samuli Ripatti and Eija H{\"a}m{\"a}l{\"a}inen and Moilanen, {Jukka S.} and Jarmo K{\"o}rkk{\"o} and Outi Kuismin and Merete Nordentoft and Hougaard, {David M.} and Ole Mors and Thomas Werge and Mortensen, {Preben Bo} and Daniel MacArthur and Daly, {Mark J.} and Sullivan, {Patrick F.} and Locke, {Adam E.} and Aarno Palotie and B{\o}rglum, {Anders D.} and Sekar Kathiresan and Neale, {Benjamin M.}",
year = "2018",
doi = "10.1016/j.ajhg.2018.05.002",
language = "English",
volume = "102",
pages = "1204--1211",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "6",
}
RIS
TY - JOUR
T1 - Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum
AU - Ganna, Andrea
AU - Satterstrom, F. Kyle
AU - Zekavat, Seyedeh M.
AU - Das, Indraniel
AU - Kurki, Mitja I.
AU - Churchhouse, Claire
AU - Alfoldi, Jessica
AU - Martin, Alicia R.
AU - Havulinna, Aki S.
AU - Byrnes, Andrea
AU - Thompson, Wesley K.
AU - Nielsen, Philip R.
AU - Karczewski, Konrad J.
AU - Saarentaus, Elmo
AU - Rivas, Manuel A.
AU - Gupta, Namrata
AU - Pietiläinen, Olli
AU - Emdin, Connor A.
AU - Lescai, Francesco
AU - Bybjerg-Grauholm, Jonas
AU - Flannick, Jason
AU - GoT2D/T2D-GENES Consortium
AU - Mercader, Josep M.
AU - Udler, Miriam
AU - SIGMA Consortium Helmsley IBD Exome Sequencing Project
AU - FinMetSeq Consortium
AU - iPSYCH-Broad Consortium
AU - Laakso, Markku
AU - Salomaa, Veikko
AU - Hultman, Christina
AU - Ripatti, Samuli
AU - Hämäläinen, Eija
AU - Moilanen, Jukka S.
AU - Körkkö, Jarmo
AU - Kuismin, Outi
AU - Nordentoft, Merete
AU - Hougaard, David M.
AU - Mors, Ole
AU - Werge, Thomas
AU - Mortensen, Preben Bo
AU - MacArthur, Daniel
AU - Daly, Mark J.
AU - Sullivan, Patrick F.
AU - Locke, Adam E.
AU - Palotie, Aarno
AU - Børglum, Anders D.
AU - Kathiresan, Sekar
AU - Neale, Benjamin M.
PY - 2018
Y1 - 2018
N2 - There is a limited understanding about the impact of rare protein-truncating variants across multiple phenotypes. We explore the impact of this class of variants on 13 quantitative traits and 10 diseases using whole-exome sequencing data from 100,296 individuals. Protein-truncating variants in genes intolerant to this class of mutations increased risk of autism, schizophrenia, bipolar disorder, intellectual disability, and ADHD. In individuals without these disorders, there was an association with shorter height, lower education, increased hospitalization, and reduced age at enrollment. Gene sets implicated from GWASs did not show a significant protein-truncating variants burden beyond what was captured by established Mendelian genes. In conclusion, we provide a thorough investigation of the impact of rare deleterious coding variants on complex traits, suggesting widespread pleiotropic risk.
AB - There is a limited understanding about the impact of rare protein-truncating variants across multiple phenotypes. We explore the impact of this class of variants on 13 quantitative traits and 10 diseases using whole-exome sequencing data from 100,296 individuals. Protein-truncating variants in genes intolerant to this class of mutations increased risk of autism, schizophrenia, bipolar disorder, intellectual disability, and ADHD. In individuals without these disorders, there was an association with shorter height, lower education, increased hospitalization, and reduced age at enrollment. Gene sets implicated from GWASs did not show a significant protein-truncating variants burden beyond what was captured by established Mendelian genes. In conclusion, we provide a thorough investigation of the impact of rare deleterious coding variants on complex traits, suggesting widespread pleiotropic risk.
KW - burden analysis
KW - constraint genes
KW - exome sequencing
KW - phewas
KW - rare variants
KW - selection
KW - ultra-rare variants
U2 - 10.1016/j.ajhg.2018.05.002
DO - 10.1016/j.ajhg.2018.05.002
M3 - Journal article
C2 - 29861106
AN - SCOPUS:85047311473
VL - 102
SP - 1204
EP - 1211
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 6
ER -
