Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients

Abstract With polygenic risk score (PRS) for autoimmune type 1 diabetes (T1D), this study identified T1D cases with low T1D PRS and searched for susceptibility loci in these cases. Our hypothesis is that genetic effects (likely mediated by relatively rare genetic variants) of non-mainstream (or non-...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jingchun Qu, Hui-Qi Qu, Jonathan P. Bradfield, Joseph T. Glessner, Xiao Chang, Lifeng Tian, Michael March, John J. Connolly, Jeffrey D. Roizen, Patrick M. A. Sleiman, Hakon Hakonarson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ed9a2299120543618940a4496e3810ca
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ed9a2299120543618940a4496e3810ca
record_format	dspace
spelling	oai:doaj.org-article:ed9a2299120543618940a4496e3810ca2021-12-02T14:53:43ZInsights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients10.1038/s41598-021-94994-92045-2322https://doaj.org/article/ed9a2299120543618940a4496e3810ca2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94994-9https://doaj.org/toc/2045-2322Abstract With polygenic risk score (PRS) for autoimmune type 1 diabetes (T1D), this study identified T1D cases with low T1D PRS and searched for susceptibility loci in these cases. Our hypothesis is that genetic effects (likely mediated by relatively rare genetic variants) of non-mainstream (or non-autoimmune) T1D might have been diluted in the previous studies on T1D cases in general. Two cohorts for the PRS modeling and testing respectively were included. The first cohort consisted of 3302 T1D cases and 6181 controls, and the independent second cohort consisted of 3297 T1D cases and 6169 controls. Cases with low T1D PRS were identified using PRSice-2 and compared to controls with low T1D PRS by genome-wide association (GWA) test. Thirteen novel genetic loci with high imputation quality (Quality Score r2 > 0.91) were identified of SNPs/SNVs associated with low PRS T1D at genome-wide significance (P ≤ 5.0 × E−08), in addition to 4 established T1D loci, 3 reported loci by our previous study, as well as 9 potential novel loci represented by rare SNVs, but with relatively low imputation quality (Quality Score r2 < 0.90). For the 13 novel loci, 9 regions have been reported of association with obesity related traits by previous GWA studies. Three loci encoding long intergenic non-protein coding RNAs (lncRNA), and 2 loci involved in N-linked glycosylation are also highlighted in this study.Jingchun QuHui-Qi QuJonathan P. BradfieldJoseph T. GlessnerXiao ChangLifeng TianMichael MarchJohn J. ConnollyJeffrey D. RoizenPatrick M. A. SleimanHakon HakonarsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jingchun Qu Hui-Qi Qu Jonathan P. Bradfield Joseph T. Glessner Xiao Chang Lifeng Tian Michael March John J. Connolly Jeffrey D. Roizen Patrick M. A. Sleiman Hakon Hakonarson Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients
description	Abstract With polygenic risk score (PRS) for autoimmune type 1 diabetes (T1D), this study identified T1D cases with low T1D PRS and searched for susceptibility loci in these cases. Our hypothesis is that genetic effects (likely mediated by relatively rare genetic variants) of non-mainstream (or non-autoimmune) T1D might have been diluted in the previous studies on T1D cases in general. Two cohorts for the PRS modeling and testing respectively were included. The first cohort consisted of 3302 T1D cases and 6181 controls, and the independent second cohort consisted of 3297 T1D cases and 6169 controls. Cases with low T1D PRS were identified using PRSice-2 and compared to controls with low T1D PRS by genome-wide association (GWA) test. Thirteen novel genetic loci with high imputation quality (Quality Score r2 > 0.91) were identified of SNPs/SNVs associated with low PRS T1D at genome-wide significance (P ≤ 5.0 × E−08), in addition to 4 established T1D loci, 3 reported loci by our previous study, as well as 9 potential novel loci represented by rare SNVs, but with relatively low imputation quality (Quality Score r2 < 0.90). For the 13 novel loci, 9 regions have been reported of association with obesity related traits by previous GWA studies. Three loci encoding long intergenic non-protein coding RNAs (lncRNA), and 2 loci involved in N-linked glycosylation are also highlighted in this study.
format	article
author	Jingchun Qu Hui-Qi Qu Jonathan P. Bradfield Joseph T. Glessner Xiao Chang Lifeng Tian Michael March John J. Connolly Jeffrey D. Roizen Patrick M. A. Sleiman Hakon Hakonarson
author_facet	Jingchun Qu Hui-Qi Qu Jonathan P. Bradfield Joseph T. Glessner Xiao Chang Lifeng Tian Michael March John J. Connolly Jeffrey D. Roizen Patrick M. A. Sleiman Hakon Hakonarson
author_sort	Jingchun Qu
title	Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients
title_short	Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients
title_full	Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients
title_fullStr	Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients
title_full_unstemmed	Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients
title_sort	insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ed9a2299120543618940a4496e3810ca
work_keys_str_mv	AT jingchunqu insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT huiqiqu insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT jonathanpbradfield insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT josephtglessner insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT xiaochang insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT lifengtian insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT michaelmarch insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT johnjconnolly insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT jeffreydroizen insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT patrickmasleiman insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients AT hakonhakonarson insightsintononautoimmunetype1diabeteswith13novellociinlowpolygenicriskscorepatients
_version_	1718389421894533120

Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients

Ejemplares similares