期刊
MOLECULAR PSYCHIATRY
卷 21, 期 6, 页码 837-843出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2015.120
关键词
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资金
- National Institutes of Health [R01 MH079800, P50 MH080173, RC2 MH089964, R01 MH080912, K23 MH077807, K01 MH085812, R01 MH100141]
- University of Crete [E.L.K.E. 1348]
- Research Council of Norway [213837, 223273, 154313/V50, 177458/V50]
- South-East Norway Health Authority [2013-123]
- K.G. Jebsen Foundation
- Bergen Research Foundation
- University of Bergen
- Research Council of Norway (FUGE, Psykisk Helse)
- Helse Vest RHF
- Dr Einar Martens Fund
- BBSRC [BB/F019394/1, BB/K000195/1, BB/F022441/1] Funding Source: UKRI
- MRC [G0600237, MR/K002279/1, G0700704, G0900753, G0901461, G0100594] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K000195/1, BB/F022441/1, BB/F019394/1] Funding Source: researchfish
- Chief Scientist Office [ETM/55] Funding Source: researchfish
- Medical Research Council [G0600237, MR/K002279/1, G0700704, G0900753, MR/K026992/1, G0100594, G0901461] Funding Source: researchfish
Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P = 0.003-0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time.
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