Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.
A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so thei...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003583&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850183084788416512 |
|---|---|
| author | Brendan J Keating Sam Tischfield Sarah S Murray Tushar Bhangale Thomas S Price Joseph T Glessner Luana Galver Jeffrey C Barrett Struan F A Grant Deborah N Farlow Hareesh R Chandrupatla Mark Hansen Saad Ajmal George J Papanicolaou Yiran Guo Mingyao Li Stephanie Derohannessian Paul I W de Bakker Swneke D Bailey Alexandre Montpetit Andrew C Edmondson Kent Taylor Xiaowu Gai Susanna S Wang Myriam Fornage Tamim Shaikh Leif Groop Michael Boehnke Alistair S Hall Andrew T Hattersley Edward Frackelton Nick Patterson Charleston W K Chiang Cecelia E Kim Richard R Fabsitz Willem Ouwehand Alkes L Price Patricia Munroe Mark Caulfield Thomas Drake Eric Boerwinkle David Reich A Stephen Whitehead Thomas P Cappola Nilesh J Samani A Jake Lusis Eric Schadt James G Wilson Wolfgang Koenig Mark I McCarthy Sekar Kathiresan Stacey B Gabriel Hakon Hakonarson Sonia S Anand Muredach Reilly James C Engert Deborah A Nickerson Daniel J Rader Joel N Hirschhorn Garret A Fitzgerald |
| author_facet | Brendan J Keating Sam Tischfield Sarah S Murray Tushar Bhangale Thomas S Price Joseph T Glessner Luana Galver Jeffrey C Barrett Struan F A Grant Deborah N Farlow Hareesh R Chandrupatla Mark Hansen Saad Ajmal George J Papanicolaou Yiran Guo Mingyao Li Stephanie Derohannessian Paul I W de Bakker Swneke D Bailey Alexandre Montpetit Andrew C Edmondson Kent Taylor Xiaowu Gai Susanna S Wang Myriam Fornage Tamim Shaikh Leif Groop Michael Boehnke Alistair S Hall Andrew T Hattersley Edward Frackelton Nick Patterson Charleston W K Chiang Cecelia E Kim Richard R Fabsitz Willem Ouwehand Alkes L Price Patricia Munroe Mark Caulfield Thomas Drake Eric Boerwinkle David Reich A Stephen Whitehead Thomas P Cappola Nilesh J Samani A Jake Lusis Eric Schadt James G Wilson Wolfgang Koenig Mark I McCarthy Sekar Kathiresan Stacey B Gabriel Hakon Hakonarson Sonia S Anand Muredach Reilly James C Engert Deborah A Nickerson Daniel J Rader Joel N Hirschhorn Garret A Fitzgerald |
| author_sort | Brendan J Keating |
| collection | DOAJ |
| description | A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions. |
| format | Article |
| id | doaj-art-20a3c01d6d394132abfac9f27abb03be |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-20a3c01d6d394132abfac9f27abb03be2025-08-20T02:17:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01310e358310.1371/journal.pone.0003583Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.Brendan J KeatingSam TischfieldSarah S MurrayTushar BhangaleThomas S PriceJoseph T GlessnerLuana GalverJeffrey C BarrettStruan F A GrantDeborah N FarlowHareesh R ChandrupatlaMark HansenSaad AjmalGeorge J PapanicolaouYiran GuoMingyao LiStephanie DerohannessianPaul I W de BakkerSwneke D BaileyAlexandre MontpetitAndrew C EdmondsonKent TaylorXiaowu GaiSusanna S WangMyriam FornageTamim ShaikhLeif GroopMichael BoehnkeAlistair S HallAndrew T HattersleyEdward FrackeltonNick PattersonCharleston W K ChiangCecelia E KimRichard R FabsitzWillem OuwehandAlkes L PricePatricia MunroeMark CaulfieldThomas DrakeEric BoerwinkleDavid ReichA Stephen WhiteheadThomas P CappolaNilesh J SamaniA Jake LusisEric SchadtJames G WilsonWolfgang KoenigMark I McCarthySekar KathiresanStacey B GabrielHakon HakonarsonSonia S AnandMuredach ReillyJames C EngertDeborah A NickersonDaniel J RaderJoel N HirschhornGarret A FitzgeraldA wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003583&type=printable |
| spellingShingle | Brendan J Keating Sam Tischfield Sarah S Murray Tushar Bhangale Thomas S Price Joseph T Glessner Luana Galver Jeffrey C Barrett Struan F A Grant Deborah N Farlow Hareesh R Chandrupatla Mark Hansen Saad Ajmal George J Papanicolaou Yiran Guo Mingyao Li Stephanie Derohannessian Paul I W de Bakker Swneke D Bailey Alexandre Montpetit Andrew C Edmondson Kent Taylor Xiaowu Gai Susanna S Wang Myriam Fornage Tamim Shaikh Leif Groop Michael Boehnke Alistair S Hall Andrew T Hattersley Edward Frackelton Nick Patterson Charleston W K Chiang Cecelia E Kim Richard R Fabsitz Willem Ouwehand Alkes L Price Patricia Munroe Mark Caulfield Thomas Drake Eric Boerwinkle David Reich A Stephen Whitehead Thomas P Cappola Nilesh J Samani A Jake Lusis Eric Schadt James G Wilson Wolfgang Koenig Mark I McCarthy Sekar Kathiresan Stacey B Gabriel Hakon Hakonarson Sonia S Anand Muredach Reilly James C Engert Deborah A Nickerson Daniel J Rader Joel N Hirschhorn Garret A Fitzgerald Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. PLoS ONE |
| title | Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. |
| title_full | Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. |
| title_fullStr | Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. |
| title_full_unstemmed | Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. |
| title_short | Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. |
| title_sort | concept design and implementation of a cardiovascular gene centric 50 k snp array for large scale genomic association studies |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003583&type=printable |
| work_keys_str_mv | AT brendanjkeating conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT samtischfield conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT sarahsmurray conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT tusharbhangale conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT thomassprice conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT josephtglessner conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT luanagalver conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT jeffreycbarrett conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT struanfagrant conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT deborahnfarlow conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT hareeshrchandrupatla conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT markhansen conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT saadajmal conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT georgejpapanicolaou conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT yiranguo conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT mingyaoli conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT stephaniederohannessian conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT pauliwdebakker conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT swnekedbailey conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT alexandremontpetit conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT andrewcedmondson conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT kenttaylor conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT xiaowugai conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT susannaswang conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT myriamfornage conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT tamimshaikh conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT leifgroop conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT michaelboehnke conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT alistairshall conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT andrewthattersley conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT edwardfrackelton conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT nickpatterson conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT charlestonwkchiang conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT ceceliaekim conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT richardrfabsitz conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT willemouwehand conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT alkeslprice conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT patriciamunroe conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT markcaulfield conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT thomasdrake conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT ericboerwinkle conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT davidreich conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT astephenwhitehead conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT thomaspcappola conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT nileshjsamani conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT ajakelusis conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT ericschadt conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT jamesgwilson conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT wolfgangkoenig conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT markimccarthy conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT sekarkathiresan conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT staceybgabriel conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT hakonhakonarson conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT soniasanand conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT muredachreilly conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT jamescengert conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT deborahanickerson conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT danieljrader conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT joelnhirschhorn conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies AT garretafitzgerald conceptdesignandimplementationofacardiovasculargenecentric50ksnparrayforlargescalegenomicassociationstudies |