Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

Robert Power; Craig Nagoshi; John C Defries; Peter Donnelly; Ines Barroso; Jenefer M Blackwell; Elvira Bramon; Matthew A Brown; Juan P Casas; Aiden Corvin; Panos Deloukas; Audrey Duncanson; Janusz Jankowski; Hugh S Markus; Christopher G Mathew; Colin Na Palmer; Anna Rautanen; Stephen J Sawcer; Richard C Trembath; Ananth C Viswanathan; Nicholas W Wood; Chris C A Spencer; Gavin Band; C??line Bellenguez; Colin Freeman; Garrett Hellenthal; Eleni Giannoulatou; Matti Pirinen; Richard Pearson; Amy Strange; Zhan Su; Damjan Vukcevic; Peter Donnelly; Cordelia Langford; Sarah E Hunt; Sarah Edkins; Rhian Gwilliam; Hannah Blackburn; Suzannah J Bumpstead; Serge Dronov; Matthew Gillman; Emma Gray; Naomi Hammond; Alagurevathi Jayakumar; Owen T Mccann; Jennifer Liddle; Simon C Potter; Radhi Ravindrarajah; Michelle Ricketts; Matthew Waller; Paul Weston; Sara Widaa; Pamela Whittaker; Ines Barroso; Panos Deloukas; Christopher G Mathew; Jenefer M Blackwell; Matthew A Brown; Aiden Corvin; Chris C A Spencer; Robert Plomin

doi:10.1038/ejhg.2013.155

Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

Robert Power, Craig Nagoshi, John C Defries, Peter Donnelly, Ines Barroso, Jenefer M Blackwell, Elvira Bramon, Matthew A Brown, Juan P Casas, Aiden Corvin, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S Markus, Christopher G Mathew, Colin Na Palmer, Anna Rautanen, Stephen J Sawcer, Richard C Trembath, Ananth C ViswanathanNicholas W Wood, Chris C A Spencer, Gavin Band, C??line Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, Cordelia Langford, Sarah E Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T Mccann, Jennifer Liddle, Simon C Potter, Radhi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Ines Barroso, Panos Deloukas, Christopher G Mathew, Jenefer M Blackwell, Matthew A Brown, Aiden Corvin, Chris C A Spencer, Robert Plomin

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

The consequence of reduced cognitive ability from inbreeding has long been investigated, mainly restricted to cousin–cousin marriages. Molecular genetic techniques now allow us to test the relationship between increased ancestral inbreeding and cognitive ability in a population of traditionally unrelated individuals. In a representative UK sample of 2329 individuals, we used genome-wide SNP data to estimate the percentage of the genome covered by runs of homozygous SNPs (ROH). This was tested for association with general cognitive ability, as well as measures of verbal and non-verbal ability. Further, association was tested between these traits and specific ROH. Burden of ROH was not associated with cognitive ability after correction for multiple testing, although burden of ROH was nominally associated with increased non-verbal cognitive ability (P=0.03). Moreover, although no individual ROH was significantly associated with cognitive ability, there was a significant bias towards increased cognitive ability in carriers of ROH (P=0.002). A potential explanation for these results is increased positive assortative mating in spouses with higher cognitive ability, although we found no evidence in support of this hypothesis in a separate sample. Reduced minor allele frequency across the genome was associated with higher cognitive ability, which could contribute to an apparent increase in ROH. This may reflect minor alleles being more likely to be deleterious.

Original language	English
Pages (from-to)	386-390
Number of pages	5
Journal	European Journal of Human Genetics
Volume	22
Issue number	3
DOIs	https://doi.org/10.1038/ejhg.2013.155
Publication status	Published - Mar 2014

Keywords

Intelligence
Assortative mating
Inbreeding
Runs of homozygosity
Genome-wide association study
Cognitive ability

Access to Document

10.1038/ejhg.2013.155

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925279/

GHCA: Genetics of High Cognitive Abilities
Plomin, R. (Primary Investigator)
EC European Commission
1/04/2012 → 31/03/2017
Project: Research
Non-Clinical Research Professorship.
Plomin, R. (Primary Investigator)
MRC Medical Research Council
1/10/2010 → 30/09/2015
Project: Research
Origins of learning difficulties and behaviour problems: from behavioural genetics to behavioural genomics
Plomin, R. (Primary Investigator)
MRC Medical Research Council
1/10/2010 → 30/09/2015
Project: Research

Cite this

Power, R., Nagoshi, C., Defries, J. C., Donnelly, P., Barroso, I., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Deloukas, P., Duncanson, A., Jankowski, J., Markus, H. S., Mathew, C. G., Palmer, C. N., Rautanen, A., Sawcer, S. J., Trembath, R. C., ... Plomin, R. (2014). Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability. European Journal of Human Genetics, 22(3), 386-390. https://doi.org/10.1038/ejhg.2013.155

@article{6b7e42b40e4c43928cf1ff22fc2a5d5d,

title = "Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability",

abstract = "The consequence of reduced cognitive ability from inbreeding has long been investigated, mainly restricted to cousin–cousin marriages. Molecular genetic techniques now allow us to test the relationship between increased ancestral inbreeding and cognitive ability in a population of traditionally unrelated individuals. In a representative UK sample of 2329 individuals, we used genome-wide SNP data to estimate the percentage of the genome covered by runs of homozygous SNPs (ROH). This was tested for association with general cognitive ability, as well as measures of verbal and non-verbal ability. Further, association was tested between these traits and specific ROH. Burden of ROH was not associated with cognitive ability after correction for multiple testing, although burden of ROH was nominally associated with increased non-verbal cognitive ability (P=0.03). Moreover, although no individual ROH was significantly associated with cognitive ability, there was a significant bias towards increased cognitive ability in carriers of ROH (P=0.002). A potential explanation for these results is increased positive assortative mating in spouses with higher cognitive ability, although we found no evidence in support of this hypothesis in a separate sample. Reduced minor allele frequency across the genome was associated with higher cognitive ability, which could contribute to an apparent increase in ROH. This may reflect minor alleles being more likely to be deleterious.",

keywords = "Intelligence, Assortative mating, Inbreeding, Runs of homozygosity, Genome-wide association study , Cognitive ability",

author = "Robert Power and Craig Nagoshi and Defries, {John C} and Peter Donnelly and Ines Barroso and Blackwell, {Jenefer M} and Elvira Bramon and Brown, {Matthew A} and Casas, {Juan P} and Aiden Corvin and Panos Deloukas and Audrey Duncanson and Janusz Jankowski and Markus, {Hugh S} and Mathew, {Christopher G} and Palmer, {Colin Na} and Anna Rautanen and Sawcer, {Stephen J} and Trembath, {Richard C} and Viswanathan, {Ananth C} and Wood, {Nicholas W} and Spencer, {Chris C A} and Gavin Band and C??line Bellenguez and Colin Freeman and Garrett Hellenthal and Eleni Giannoulatou and Matti Pirinen and Richard Pearson and Amy Strange and Zhan Su and Damjan Vukcevic and Peter Donnelly and Cordelia Langford and Hunt, {Sarah E} and Sarah Edkins and Rhian Gwilliam and Hannah Blackburn and Bumpstead, {Suzannah J} and Serge Dronov and Matthew Gillman and Emma Gray and Naomi Hammond and Alagurevathi Jayakumar and Mccann, {Owen T} and Jennifer Liddle and Potter, {Simon C} and Radhi Ravindrarajah and Michelle Ricketts and Matthew Waller and Paul Weston and Sara Widaa and Pamela Whittaker and Ines Barroso and Panos Deloukas and Mathew, {Christopher G} and Blackwell, {Jenefer M} and Brown, {Matthew A} and Aiden Corvin and Spencer, {Chris C A} and Robert Plomin",

year = "2014",

month = mar,

doi = "10.1038/ejhg.2013.155",

language = "English",

volume = "22",

pages = "386--390",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Nature Publishing Group",

number = "3",

}

Power, R, Nagoshi, C, Defries, JC, Donnelly, P, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CN, Rautanen, A, Sawcer, SJ, Trembath, RC , Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Donnelly, P, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Barroso, I, Deloukas, P, Mathew, CG, Blackwell, JM, Brown, MA, Corvin, A, Spencer, CCA & Plomin, R 2014, 'Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability', European Journal of Human Genetics, vol. 22, no. 3, pp. 386-390. https://doi.org/10.1038/ejhg.2013.155

TY - JOUR

T1 - Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

AU - Power, Robert

AU - Nagoshi, Craig

AU - Defries, John C

AU - Donnelly, Peter

AU - Barroso, Ines

AU - Blackwell, Jenefer M

AU - Bramon, Elvira

AU - Brown, Matthew A

AU - Casas, Juan P

AU - Corvin, Aiden

AU - Deloukas, Panos

AU - Duncanson, Audrey

AU - Jankowski, Janusz

AU - Markus, Hugh S

AU - Mathew, Christopher G

AU - Palmer, Colin Na

AU - Rautanen, Anna

AU - Sawcer, Stephen J

AU - Trembath, Richard C

AU - Viswanathan, Ananth C

AU - Wood, Nicholas W

AU - Spencer, Chris C A

AU - Band, Gavin

AU - Bellenguez, C??line

AU - Freeman, Colin

AU - Hellenthal, Garrett

AU - Giannoulatou, Eleni

AU - Pirinen, Matti

AU - Pearson, Richard

AU - Strange, Amy

AU - Su, Zhan

AU - Vukcevic, Damjan

AU - Donnelly, Peter

AU - Langford, Cordelia

AU - Hunt, Sarah E

AU - Edkins, Sarah

AU - Gwilliam, Rhian

AU - Blackburn, Hannah

AU - Bumpstead, Suzannah J

AU - Dronov, Serge

AU - Gillman, Matthew

AU - Gray, Emma

AU - Hammond, Naomi

AU - Jayakumar, Alagurevathi

AU - Mccann, Owen T

AU - Liddle, Jennifer

AU - Potter, Simon C

AU - Ravindrarajah, Radhi

AU - Ricketts, Michelle

AU - Waller, Matthew

AU - Weston, Paul

AU - Widaa, Sara

AU - Whittaker, Pamela

AU - Barroso, Ines

AU - Deloukas, Panos

AU - Mathew, Christopher G

AU - Blackwell, Jenefer M

AU - Brown, Matthew A

AU - Corvin, Aiden

AU - Spencer, Chris C A

AU - Plomin, Robert

PY - 2014/3

Y1 - 2014/3

N2 - The consequence of reduced cognitive ability from inbreeding has long been investigated, mainly restricted to cousin–cousin marriages. Molecular genetic techniques now allow us to test the relationship between increased ancestral inbreeding and cognitive ability in a population of traditionally unrelated individuals. In a representative UK sample of 2329 individuals, we used genome-wide SNP data to estimate the percentage of the genome covered by runs of homozygous SNPs (ROH). This was tested for association with general cognitive ability, as well as measures of verbal and non-verbal ability. Further, association was tested between these traits and specific ROH. Burden of ROH was not associated with cognitive ability after correction for multiple testing, although burden of ROH was nominally associated with increased non-verbal cognitive ability (P=0.03). Moreover, although no individual ROH was significantly associated with cognitive ability, there was a significant bias towards increased cognitive ability in carriers of ROH (P=0.002). A potential explanation for these results is increased positive assortative mating in spouses with higher cognitive ability, although we found no evidence in support of this hypothesis in a separate sample. Reduced minor allele frequency across the genome was associated with higher cognitive ability, which could contribute to an apparent increase in ROH. This may reflect minor alleles being more likely to be deleterious.

AB - The consequence of reduced cognitive ability from inbreeding has long been investigated, mainly restricted to cousin–cousin marriages. Molecular genetic techniques now allow us to test the relationship between increased ancestral inbreeding and cognitive ability in a population of traditionally unrelated individuals. In a representative UK sample of 2329 individuals, we used genome-wide SNP data to estimate the percentage of the genome covered by runs of homozygous SNPs (ROH). This was tested for association with general cognitive ability, as well as measures of verbal and non-verbal ability. Further, association was tested between these traits and specific ROH. Burden of ROH was not associated with cognitive ability after correction for multiple testing, although burden of ROH was nominally associated with increased non-verbal cognitive ability (P=0.03). Moreover, although no individual ROH was significantly associated with cognitive ability, there was a significant bias towards increased cognitive ability in carriers of ROH (P=0.002). A potential explanation for these results is increased positive assortative mating in spouses with higher cognitive ability, although we found no evidence in support of this hypothesis in a separate sample. Reduced minor allele frequency across the genome was associated with higher cognitive ability, which could contribute to an apparent increase in ROH. This may reflect minor alleles being more likely to be deleterious.

KW - Intelligence

KW - Assortative mating

KW - Inbreeding

KW - Runs of homozygosity

KW - Genome-wide association study

KW - Cognitive ability

U2 - 10.1038/ejhg.2013.155

DO - 10.1038/ejhg.2013.155

M3 - Article

SN - 1018-4813

VL - 22

SP - 386

EP - 390

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 3

ER -

Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

Abstract

Keywords

Access to Document

Fingerprint

Projects

GHCA: Genetics of High Cognitive Abilities

Non-Clinical Research Professorship.

Origins of learning difficulties and behaviour problems: from behavioural genetics to behavioural genomics

Cite this