1. Reevaluation of SNP heritability in complex human traits
- Author
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David J. Balding, Doug Speed, Na Cai, Sergey Nejentsev, Marvin Johnson, Imperial College Healthcare NHS Trust- BRC Funding, and Medical Research Council (MRC)
- Subjects
0301 basic medicine ,Multifactorial Inheritance ,Linkage disequilibrium ,Inheritance Patterns ,VARIANTS ,Biology ,Quantitative trait locus ,Polymorphism, Single Nucleotide ,Genetic correlation ,Article ,GENETIC ARCHITECTURE ,Cohort Studies ,COMMON SNPS ,03 medical and health sciences ,Quantitative Trait, Heritable ,MIXED-MODEL ,Gene Frequency ,MISSING HERITABILITY ,Missing heritability problem ,Genetics ,Deoxyribonuclease I ,Humans ,Computer Simulation ,UCLEB Consortium ,PARTITIONING HERITABILITY ,GENOME-WIDE ASSOCIATION ,Alleles ,Genetic Association Studies ,Genetics & Heredity ,Science & Technology ,Models, Genetic ,Chromosome Fragile Sites ,RESTRICTED MAXIMUM-LIKELIHOOD ,11 Medical And Health Sciences ,06 Biological Sciences ,Heritability ,Explained variation ,Genetic architecture ,RHEUMATOID-ARTHRITIS ,Minor allele frequency ,030104 developmental biology ,Case-Control Studies ,Life Sciences & Biomedicine ,HUMAN HEIGHT ,Genome-Wide Association Study ,Developmental Biology - Abstract
SNP heritability, the proportion of phenotypic variance explained by SNPs, has been reported for many hundreds of traits. Its estimation requires strong prior assumptions about the distribution of heritability across the genome, but the assumptions in current use have not been thoroughly tested. By analyzing imputed data for a large number of human traits, we empirically derive a model that more accurately describes how heritability varies with minor allele frequency, linkage disequilibrium and genotype certainty. Across 19 traits, our improved model leads to estimates of common SNP heritability on average 43% (standard deviation 3) higher than those obtained from the widely-used software GCTA, and 25% (standard deviation 2) higher than those from the recently-proposed extension GCTA-LDMS. Previously, DNaseI hypersensitivity sites were reported to explain 79% of SNP heritability; using our improved heritability model their estimated contribution is only 24%.
- Published
- 2017