Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach.

Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predic...
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Autor*in:	Oriol Canela-Xandri [verfasserIn] Konrad Rawlik [verfasserIn] John A Woolliams [verfasserIn] Albert Tenesa [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2016

Übergeordnetes Werk:	In: PLoS ONE - Public Library of Science (PLoS), 2007, 11(2016), 12, p e0166755
Übergeordnetes Werk:	volume:11 ; year:2016 ; number:12, p e0166755

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1371/journal.pone.0166755

Katalog-ID:	DOAJ014651718

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publishDate	2016
allfields	10.1371/journal.pone.0166755 doi (DE-627)DOAJ014651718 (DE-599)DOAJ35ddc098f2484824bdfc8ae3c1eb2c89 DE-627 ger DE-627 rakwb eng Oriol Canela-Xandri verfasserin aut Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF < 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models. Medicine R Science Q Konrad Rawlik verfasserin aut John A Woolliams verfasserin aut Albert Tenesa verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 11(2016), 12, p e0166755 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:11 year:2016 number:12, p e0166755 https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/article/35ddc098f2484824bdfc8ae3c1eb2c89 kostenfrei https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2016 12, p e0166755
spelling	10.1371/journal.pone.0166755 doi (DE-627)DOAJ014651718 (DE-599)DOAJ35ddc098f2484824bdfc8ae3c1eb2c89 DE-627 ger DE-627 rakwb eng Oriol Canela-Xandri verfasserin aut Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF < 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models. Medicine R Science Q Konrad Rawlik verfasserin aut John A Woolliams verfasserin aut Albert Tenesa verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 11(2016), 12, p e0166755 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:11 year:2016 number:12, p e0166755 https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/article/35ddc098f2484824bdfc8ae3c1eb2c89 kostenfrei https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2016 12, p e0166755
allfields_unstemmed	10.1371/journal.pone.0166755 doi (DE-627)DOAJ014651718 (DE-599)DOAJ35ddc098f2484824bdfc8ae3c1eb2c89 DE-627 ger DE-627 rakwb eng Oriol Canela-Xandri verfasserin aut Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF < 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models. Medicine R Science Q Konrad Rawlik verfasserin aut John A Woolliams verfasserin aut Albert Tenesa verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 11(2016), 12, p e0166755 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:11 year:2016 number:12, p e0166755 https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/article/35ddc098f2484824bdfc8ae3c1eb2c89 kostenfrei https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2016 12, p e0166755
allfieldsGer	10.1371/journal.pone.0166755 doi (DE-627)DOAJ014651718 (DE-599)DOAJ35ddc098f2484824bdfc8ae3c1eb2c89 DE-627 ger DE-627 rakwb eng Oriol Canela-Xandri verfasserin aut Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF < 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models. Medicine R Science Q Konrad Rawlik verfasserin aut John A Woolliams verfasserin aut Albert Tenesa verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 11(2016), 12, p e0166755 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:11 year:2016 number:12, p e0166755 https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/article/35ddc098f2484824bdfc8ae3c1eb2c89 kostenfrei https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2016 12, p e0166755
allfieldsSound	10.1371/journal.pone.0166755 doi (DE-627)DOAJ014651718 (DE-599)DOAJ35ddc098f2484824bdfc8ae3c1eb2c89 DE-627 ger DE-627 rakwb eng Oriol Canela-Xandri verfasserin aut Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF < 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models. Medicine R Science Q Konrad Rawlik verfasserin aut John A Woolliams verfasserin aut Albert Tenesa verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 11(2016), 12, p e0166755 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:11 year:2016 number:12, p e0166755 https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/article/35ddc098f2484824bdfc8ae3c1eb2c89 kostenfrei https://doi.org/10.1371/journal.pone.0166755 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2016 12, p e0166755
language	English
source	In PLoS ONE 11(2016), 12, p e0166755 volume:11 year:2016 number:12, p e0166755
sourceStr	In PLoS ONE 11(2016), 12, p e0166755 volume:11 year:2016 number:12, p e0166755
format_phy_str_mv	Article
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topic_facet	Medicine R Science Q
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container_title	PLoS ONE
authorswithroles_txt_mv	Oriol Canela-Xandri @@aut@@ Konrad Rawlik @@aut@@ John A Woolliams @@aut@@ Albert Tenesa @@aut@@
publishDateDaySort_date	2016-01-01T00:00:00Z
hierarchy_top_id	523574592
id	DOAJ014651718
language_de	englisch
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author	Oriol Canela-Xandri
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topic_title	Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach
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title	Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach.
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title_full	Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach
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title_sort	improved genetic profiling of anthropometric traits using a big data approach
title_auth	Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach.
abstract	Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF < 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models.
abstractGer	Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF < 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models.
abstract_unstemmed	Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF < 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models.
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title_short	Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach.
url	https://doi.org/10.1371/journal.pone.0166755 https://doaj.org/article/35ddc098f2484824bdfc8ae3c1eb2c89 https://doaj.org/toc/1932-6203
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