Beyond SNP heritability : Polygenicity and discoverability of phenotypes estimated with a univariate Gaussian mixture model
Estimating the polygenicity (proportion of causally associated single nucleotide polymorphisms (SNPs)) and discoverability (effect size variance) of causal SNPs for human traits is currently of considerable interest. SNP-heritability is proportional to the product of these quantities. We present a basic model, using detailed linkage disequilibrium structure from a reference panel of 11 million SNPs, to estimate these quantities from genome-wide association studies (GWAS) summary statistics. We apply the model to diverse phenotypes and validate the implementation with simulations. We find model polygenicities (as a fraction of the reference panel) ranging from ≃ 2 × 10-5 to ≃ 4 × 10-3, with discoverabilities similarly ranging over two orders of magnitude. A power analysis allows us to estimate the proportions of phenotypic variance explained additively by causal SNPs reaching genome-wide significance at current sample sizes, and map out sample sizes required to explain larger portions of additive SNP heritability. The model also allows for estimating residual inflation (or deflation from over-correcting of z-scores), and assessing compatibility of replication and discovery GWAS summary statistics.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
PLoS genetics - 16(2020), 5 vom: 19. Mai, Seite e1008612 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Holland, Dominic [VerfasserIn] |
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| Anmerkungen: |
Date Completed 30.07.2020 Date Revised 30.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pgen.1008612 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Beyond SNP heritability |b Polygenicity and discoverability of phenotypes estimated with a univariate Gaussian mixture model |
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| 520 | |a Estimating the polygenicity (proportion of causally associated single nucleotide polymorphisms (SNPs)) and discoverability (effect size variance) of causal SNPs for human traits is currently of considerable interest. SNP-heritability is proportional to the product of these quantities. We present a basic model, using detailed linkage disequilibrium structure from a reference panel of 11 million SNPs, to estimate these quantities from genome-wide association studies (GWAS) summary statistics. We apply the model to diverse phenotypes and validate the implementation with simulations. We find model polygenicities (as a fraction of the reference panel) ranging from ≃ 2 × 10-5 to ≃ 4 × 10-3, with discoverabilities similarly ranging over two orders of magnitude. A power analysis allows us to estimate the proportions of phenotypic variance explained additively by causal SNPs reaching genome-wide significance at current sample sizes, and map out sample sizes required to explain larger portions of additive SNP heritability. The model also allows for estimating residual inflation (or deflation from over-correcting of z-scores), and assessing compatibility of replication and discovery GWAS summary statistics | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Frei, Oleksandr |e verfasserin |4 aut | |
| 700 | 1 | |a Desikan, Rahul |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Chun-Chieh |e verfasserin |4 aut | |
| 700 | 1 | |a Shadrin, Alexey A |e verfasserin |4 aut | |
| 700 | 1 | |a Smeland, Olav B |e verfasserin |4 aut | |
| 700 | 1 | |a Sundar, V S |e verfasserin |4 aut | |
| 700 | 1 | |a Thompson, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Andreassen, Ole A |e verfasserin |4 aut | |
| 700 | 1 | |a Dale, Anders M |e verfasserin |4 aut | |
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