publication . Article . Other literature type . Preprint . 2019

Localizing components of shared transethnic genetic architecture of complex traits from GWAS summary data

Shi, Huwenbo; Burch, Kathryn S.; Johnson, Ruth; Freund, Malika K.; Kichaev, Gleb; Mancuso, Nicholas; Manuel, Astrid M.; Dong, Natalie; Pasaniuc, Bogdan;
Restricted
  • Published: 29 Nov 2019 Journal: The American Journal of Human Genetics (issn: 0002-9297, Copyright policy)
  • Publisher: Elsevier BV
Abstract
<jats:title>Abstract</jats:title><jats:p>Despite strong transethnic genetic correlations reported in the literature for many complex traits, the non-transferability of polygenic risk scores across populations suggests the presence of population-specific components of genetic architecture. We propose an approach that models GWAS summary data for one trait in two populations to estimate genome-wide proportions of population-specific/shared causal SNPs. In simulations across various genetic architectures, we show that our approach yields approximately unbiased estimates with in-sample LD and slight upward-bias with out-of-sample LD. We analyze 9 complex traits in i...
Subjects
free text keywords: Genetics(clinical), Genetics, Bayes' theorem, Population, education.field_of_study, education, Genome-wide association study, Allele frequency, Single-nucleotide polymorphism, Biology, Trait, Genetic architecture, Sample size determination
Funded by
NIH| Joint genomic and statistical analyses of schizophrenia and bipolar to decipher genetic susceptibility
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01MH115676-01A1
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Training Grant in Neurobehavioral Genetics
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2T32MH073526-06
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Integrative approaches for mapping the genetic risk of complex traits
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01HG009120-02
  • Funding stream: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
,
NIH| Quantifying and Characterizing the shared genetic contribution to common cancers
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U01CA194393-03
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Training Grant in Genomic Analysis and Interpretation
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3T32HG002536-06S1
  • Funding stream: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
47 references, page 1 of 4

Curr. Biol. 20, R166--R173 (2010).

Cavalli-Sforza, L. L., Menozzi, P. & Piazza, A. Demic expansions and human evolution. Science (80-. ).

Pritchard, J. K., Pickrell, J. K. & Coop, G. The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Curr. Biol. 20, R208--R215 (2010). [OpenAIRE]

Laland, K. N., Odling-Smee, J. & Myles, S. How culture shaped the human genome: bringing genetics and the human sciences together. Nat. Rev. Genet. 11, 137 (2010).

Am. J. Hum. Genet. 100, 635-649 (2017).

Timpson, N. J., Greenwood, C. M. T., Soranzo, N., Lawson, D. J. & Richards, J. B. Genetic architecture: the shape of the genetic contribution to human traits and disease. Nat. Rev. Genet. 19, 110 (2017). [OpenAIRE]

Gazal, S. et al. Linkage disequilibrium-dependent architecture of human complex traits shows action of negative selection. Nat. Genet. 49, 1421 (2017). [OpenAIRE]

Gazal, S. et al. Functional architecture of low-frequency variants highlights strength of negative selection across coding and non-coding annotations. Nat. Genet. 50, 1600-1607 (2018). [OpenAIRE]

Hum. Genet. (2019). doi:https://doi.org/10.1016/j.ajhg.2019.07.003 Speed, D., Hemani, G., Johnson, M. R. & Balding, D. J. Improved Heritability Estimation from Genomewide SNPs. Am. J. Hum. Genet. 91, 1011-1021 (2012).

Speed, D. et al. Reevaluation of SNP heritability in complex human traits. Nat. Genet. 49, 986 (2017).

Visscher, P. M. et al. 10 Years of GWAS Discovery: Biology, Function, and Translation. Am. J. Hum.

Genet. 101, 5-22 (2017).

Popejoy, A. B. & Fullerton, S. M. Genomics is failing on diversity. Nature 538, 161 (2016). [OpenAIRE]

Rosenberg, N. A. et al. Genome-wide association studies in diverse populations. Nat. Rev. Genet. 11, 356 (2010).

Genet. 90, 7-24 (2012).

47 references, page 1 of 4
Abstract
<jats:title>Abstract</jats:title><jats:p>Despite strong transethnic genetic correlations reported in the literature for many complex traits, the non-transferability of polygenic risk scores across populations suggests the presence of population-specific components of genetic architecture. We propose an approach that models GWAS summary data for one trait in two populations to estimate genome-wide proportions of population-specific/shared causal SNPs. In simulations across various genetic architectures, we show that our approach yields approximately unbiased estimates with in-sample LD and slight upward-bias with out-of-sample LD. We analyze 9 complex traits in i...
Subjects
free text keywords: Genetics(clinical), Genetics, Bayes' theorem, Population, education.field_of_study, education, Genome-wide association study, Allele frequency, Single-nucleotide polymorphism, Biology, Trait, Genetic architecture, Sample size determination
Funded by
NIH| Joint genomic and statistical analyses of schizophrenia and bipolar to decipher genetic susceptibility
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01MH115676-01A1
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Training Grant in Neurobehavioral Genetics
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2T32MH073526-06
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Integrative approaches for mapping the genetic risk of complex traits
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01HG009120-02
  • Funding stream: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
,
NIH| Quantifying and Characterizing the shared genetic contribution to common cancers
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U01CA194393-03
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Training Grant in Genomic Analysis and Interpretation
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3T32HG002536-06S1
  • Funding stream: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
47 references, page 1 of 4

Curr. Biol. 20, R166--R173 (2010).

Cavalli-Sforza, L. L., Menozzi, P. & Piazza, A. Demic expansions and human evolution. Science (80-. ).

Pritchard, J. K., Pickrell, J. K. & Coop, G. The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Curr. Biol. 20, R208--R215 (2010). [OpenAIRE]

Laland, K. N., Odling-Smee, J. & Myles, S. How culture shaped the human genome: bringing genetics and the human sciences together. Nat. Rev. Genet. 11, 137 (2010).

Am. J. Hum. Genet. 100, 635-649 (2017).

Timpson, N. J., Greenwood, C. M. T., Soranzo, N., Lawson, D. J. & Richards, J. B. Genetic architecture: the shape of the genetic contribution to human traits and disease. Nat. Rev. Genet. 19, 110 (2017). [OpenAIRE]

Gazal, S. et al. Linkage disequilibrium-dependent architecture of human complex traits shows action of negative selection. Nat. Genet. 49, 1421 (2017). [OpenAIRE]

Gazal, S. et al. Functional architecture of low-frequency variants highlights strength of negative selection across coding and non-coding annotations. Nat. Genet. 50, 1600-1607 (2018). [OpenAIRE]

Hum. Genet. (2019). doi:https://doi.org/10.1016/j.ajhg.2019.07.003 Speed, D., Hemani, G., Johnson, M. R. & Balding, D. J. Improved Heritability Estimation from Genomewide SNPs. Am. J. Hum. Genet. 91, 1011-1021 (2012).

Speed, D. et al. Reevaluation of SNP heritability in complex human traits. Nat. Genet. 49, 986 (2017).

Visscher, P. M. et al. 10 Years of GWAS Discovery: Biology, Function, and Translation. Am. J. Hum.

Genet. 101, 5-22 (2017).

Popejoy, A. B. & Fullerton, S. M. Genomics is failing on diversity. Nature 538, 161 (2016). [OpenAIRE]

Rosenberg, N. A. et al. Genome-wide association studies in diverse populations. Nat. Rev. Genet. 11, 356 (2010).

Genet. 90, 7-24 (2012).

47 references, page 1 of 4
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