Ubiquitous Polygenicity of Human Complex Traits: Genome-Wide Analysis of 49 Traits in Koreans
Recent studies in population of European ancestry have shown that 30%∼50% of heritability for human complex traits such as height and body mass index, and common diseases such as schizophrenia and rheumatoid arthritis, can be captured by common SNPs and that genetic variation attributed to chromosomes are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analysed 49 human quantitative traits, many of which are relevant to human diseases, in 7,170 unrelated Korean individuals genotyped on 326,262 SNPs. For 43 of the 49 traits, we estimated a nominally significant (P<0.05) proportion of variance explained by all SNPs on the Affymetrix 5.0 genotyping array (). On average across 47 of the 49 traits for which the estimate of is non-zero, common SNPs explain approximately one-third (range of 7.8% to 76.8%) of narrow sense heritability.
The estimate of is highly correlated with the proportion of SNPs with association P<0.031 (r2 = 0.92). Longer genomic segments tend to explain more phenotypic variation, with a correlation of 0.78 between the estimate of variance explained by individual chromosomes and their physical length, and 1% of the genome explains approximately 1% of the genetic variance. Despite the fact that there are a few SNPs with large effects for some traits, these results suggest that polygenicity is ubiquitous for most human complex traits and that a substantial proportion of the “missing heritability” is captured by common SNPs.
Vyšlo v časopise:
Ubiquitous Polygenicity of Human Complex Traits: Genome-Wide Analysis of 49 Traits in Koreans. PLoS Genet 9(3): e32767. doi:10.1371/journal.pgen.1003355
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003355
Souhrn
Recent studies in population of European ancestry have shown that 30%∼50% of heritability for human complex traits such as height and body mass index, and common diseases such as schizophrenia and rheumatoid arthritis, can be captured by common SNPs and that genetic variation attributed to chromosomes are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analysed 49 human quantitative traits, many of which are relevant to human diseases, in 7,170 unrelated Korean individuals genotyped on 326,262 SNPs. For 43 of the 49 traits, we estimated a nominally significant (P<0.05) proportion of variance explained by all SNPs on the Affymetrix 5.0 genotyping array (). On average across 47 of the 49 traits for which the estimate of is non-zero, common SNPs explain approximately one-third (range of 7.8% to 76.8%) of narrow sense heritability.
The estimate of is highly correlated with the proportion of SNPs with association P<0.031 (r2 = 0.92). Longer genomic segments tend to explain more phenotypic variation, with a correlation of 0.78 between the estimate of variance explained by individual chromosomes and their physical length, and 1% of the genome explains approximately 1% of the genetic variance. Despite the fact that there are a few SNPs with large effects for some traits, these results suggest that polygenicity is ubiquitous for most human complex traits and that a substantial proportion of the “missing heritability” is captured by common SNPs.
Zdroje
1. HindorffLA, SethupathyP, JunkinsHA, RamosEM, MehtaJP, et al. (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106: 9362–9367.
2. VisscherPM, BrownMA, McCarthyMI, YangJ (2012) Five years of GWAS discovery. Am J Hum Genet 90: 7–24.
3. ManolioTA, CollinsFS, CoxNJ, GoldsteinDB, HindorffLA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747–753.
4. MaherB (2008) Personal genomes: The case of the missing heritability. Nature 456: 18–21.
5. Lango AllenH, EstradaK, LettreG, BerndtSI, WeedonMN, et al. (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467: 832–838.
6. SpeliotesEK, WillerCJ, BerndtSI, MondaKL, ThorleifssonG, et al. (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42: 937–948.
7. VisscherPM, HillWG, WrayNR (2008) Heritability in the genomics era–concepts and misconceptions. Nat Rev Genet 9: 255–266.
8. MagnussonPK, RasmussenF (2002) Familial resemblance of body mass index and familial risk of high and low body mass index. A study of young men in Sweden. Int J Obes Relat Metab Disord 26: 1225–1231.
9. SchousboeK, WillemsenG, KyvikKO, MortensenJ, BoomsmaDI, et al. (2003) Sex differences in heritability of BMI: a comparative study of results from twin studies in eight countries. Twin Res 6: 409–421.
10. YangJ, BenyaminB, McEvoyBP, GordonS, HendersAK, et al. (2010) Common SNPs explain a large proportion of the heritability for human height. Nat Genet 42: 565–569.
11. YangJ, ManolioTA, PasqualeLR, BoerwinkleE, CaporasoN, et al. (2011) Genome partitioning of genetic variation for complex traits using common SNPs. Nat Genet 43: 519–525.
12. LeeSH, DecandiaTR, RipkeS, YangJ, SullivanPF, et al. (2012) Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat Genet 44: 247–250.
13. StahlEA, WegmannD, TrynkaG, Gutierrez-AchuryJ, DoR, et al. (2012) Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat Genet 44: 483–489.
14. YangJ, LeeSH, GoddardME, VisscherPM (2011) GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 88: 76–82.
15. ChoYS, GoMJ, KimYJ, HeoJY, OhJH, et al. (2009) A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 41: 527–534.
16. DaviesG, TenesaA, PaytonA, YangJ, HarrisSE, et al. (2011) Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Mol Psychiatry 16: 996–1005.
17. DearyIJ, YangJ, DaviesG, HarrisSE, TenesaA, et al. (2012) Genetic contributions to stability and change in intelligence from childhood to old age. Nature 482: 212–215.
18. PurcellS, NealeB, Todd-BrownK, ThomasL, FerreiraMA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559–575.
19. The International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851–861.
20. AltshulerDM, GibbsRA, PeltonenL, AltshulerDM, GibbsRA, et al. (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467: 52–58.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2013 Číslo 3
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Fine Characterisation of a Recombination Hotspot at the Locus and Resolution of the Paradoxical Excess of Duplications over Deletions in the General Population
- Molecular Networks of Human Muscle Adaptation to Exercise and Age
- Recurrent Rearrangement during Adaptive Evolution in an Interspecific Yeast Hybrid Suggests a Model for Rapid Introgression
- Genome-Wide Association Study and Gene Expression Analysis Identifies as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis