Genome-wide autozygosity is associated with lower general cognitive ability

Howrigan, D.P., Simonson, M.A., Davies, G., Harris, S.E., Tenesa, A., Starr, J.M., Liewald, D.C., Deary, I.J., McRae, A., Wright, M.J., Montgomery, G.W., Hansell, N., Martin, N.G., Payton, A., Horan, M., Ollier, W.E., Abdellaoui, A., Boomsma, D.I., DeRosse, P., Knowles, E.E.M., Glahn, D.C., Djurovic, S., Melle, I., Andreassen, O.A., Christoforou, A., Steen, V.M., Hellard, S.L., Sundet, K., Reinvang, I., Espeseth, T., Lundervold, A.J., Giegling, I., Konte, B., Hartmann, A.M., Rujescu, D., Roussos, P., Giakoumaki, S., Burdick, K.E., Bitsios, P., Donohoe, G., Corley, R.P., Visscher, P.M., Pendleton, N., Malhotra, A.K., Neale, B.M., Lencz, T. and Keller, M.C. (2015) Genome-wide autozygosity is associated with lower general cognitive ability. Molecular Psychiatry, 21 6: 837-843. doi:10.1038/mp.2015.120

Author Howrigan, D.P.
Simonson, M.A.
Davies, G.
Harris, S.E.
Tenesa, A.
Starr, J.M.
Liewald, D.C.
Deary, I.J.
McRae, A.
Wright, M.J.
Montgomery, G.W.
Hansell, N.
Martin, N.G.
Payton, A.
Horan, M.
Ollier, W.E.
Abdellaoui, A.
Boomsma, D.I.
DeRosse, P.
Knowles, E.E.M.
Glahn, D.C.
Djurovic, S.
Melle, I.
Andreassen, O.A.
Christoforou, A.
Steen, V.M.
Hellard, S.L.
Sundet, K.
Reinvang, I.
Espeseth, T.
Lundervold, A.J.
Giegling, I.
Konte, B.
Hartmann, A.M.
Rujescu, D.
Roussos, P.
Giakoumaki, S.
Burdick, K.E.
Bitsios, P.
Donohoe, G.
Corley, R.P.
Visscher, P.M.
Pendleton, N.
Malhotra, A.K.
Neale, B.M.
Lencz, T.
Keller, M.C.
Title Genome-wide autozygosity is associated with lower general cognitive ability
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
Publication date 2015-09-22
Year available 2015
Sub-type Article (original research)
DOI 10.1038/mp.2015.120
Open Access Status Not yet assessed
Volume 21
Issue 6
Start page 837
End page 843
Total pages 7
Place of publication London,United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1312 Molecular Biology
2738 Psychiatry and Mental health
2804 Cellular and Molecular Neuroscience
Abstract 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.
Keyword Biochemistry & Molecular Biology
Biochemistry & Molecular Biology
Neurosciences & Neurology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID ETM/55
K01 MH085812
R01 MH100125
R01 MH100141
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
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