Journal
TRANSLATIONAL PSYCHIATRY
Volume 2, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/tp.2012.27
Keywords
complex traits; GCTA; genome-wide; polymorphisms; variance
Categories
Funding
- Australian National Health and Medical Research Council (NHMRC) [496688, 613608]
- Australian Research Council (ARC) [FT0991360]
- UK's Biotechnology and Biological Sciences Research Council (BBSRC)
- BBSRC
- The Royal Society
- The Chief Scientist Office of the Scottish Government
- Research Into Ageing
- Welcome Trust
- Alzheimer's Research Trust
- Social Science Research Council
- Medical Research Council
- Economic and Social Research Council
- Unilever plc
- United States Public Health Service [R01 DA05147, R01 AA09367, R01 AA11886, R01 DA13240, U01 DA024417]
- United States NIH [U01 DK066134]
- Swedish Ministry of Higher Education
- Biotechnology and Biological Sciences Research Council [BB/F019394/1, BB/F022441/1] Funding Source: researchfish
- Chief Scientist Office [CZB/4/505, ETM/55] Funding Source: researchfish
- Medical Research Council [G0600237, G0700704, G0900753, G0700704B, G0100594, G0901461] Funding Source: researchfish
- BBSRC [BB/F019394/1, BB/F022441/1] Funding Source: UKRI
- MRC [G0900753, G0700704, G0600237, G0901461, G0100594] Funding Source: UKRI
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The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (< similar to 2%). Using genome-wide single-nucleotide polymorphism (SNP) data from similar to 12 000 unrelated individuals we estimated the proportion of phenotypic variance explained by variants in linkage disequilibrium with common SNPs as 0.06 (s.e. = 0.03) for neuroticism and 0.12 (s.e. = 0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits similar to 45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called 'missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors. Translational Psychiatry (2012) 2, e102; doi:10.1038/tp.2012.27; published online 17 April 2012
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