Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

Lorna M. Lopez; Sarah E. Harris; Michelle Luciano; Dave Liewald; Gail Davies; Alan J. Gow; Albert Tenesa; Antony Payton; Xiayi Ke; Lawrence J. Whalley; Helen Fox; Paul Haggerty; William Ollier; Andrew Pickles; David J. Porteous; Michael A. Horan; Neil Pendleton; John M. Starr; Ian J. Deary

doi:10.1038/ejhg.2011.201

Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

Lorna M. Lopez, Sarah E. Harris, Michelle Luciano, Dave Liewald, Gail Davies, Alan J. Gow, Albert Tenesa, Antony Payton, Xiayi Ke, Lawrence J. Whalley, Helen Fox, Paul Haggerty, William Ollier, Andrew Pickles, David J. Porteous, Michael A. Horan, Neil Pendleton, John M. Starr, Ian J. Deary

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24 Citations (Scopus)

Abstract

Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. European Journal of Human Genetics (2012) 20, 341-347; doi:10.1038/ejhg.2011.201; published online 2 November 2011

Original language	English
Pages (from-to)	341 - 347
Number of pages	7
Journal	European Journal of Human Genetics
Volume	20
Issue number	3
DOIs	https://doi.org/10.1038/ejhg.2011.201
Publication status	Published - Mar 2012

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Lopez, L. M., Harris, S. E., Luciano, M., Liewald, D., Davies, G., Gow, A. J., Tenesa, A., Payton, A., Ke, X., Whalley, L. J., Fox, H., Haggerty, P., Ollier, W., Pickles, A., Porteous, D. J., Horan, M. A., Pendleton, N., Starr, J. M., & Deary, I. J. (2012). Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts. European Journal of Human Genetics, 20(3), 341 - 347. https://doi.org/10.1038/ejhg.2011.201

@article{4fb3f7a051ba41438c9466eca465da8d,

title = "Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts",

abstract = "Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. European Journal of Human Genetics (2012) 20, 341-347; doi:10.1038/ejhg.2011.201; published online 2 November 2011",

author = "Lopez, {Lorna M.} and Harris, {Sarah E.} and Michelle Luciano and Dave Liewald and Gail Davies and Gow, {Alan J.} and Albert Tenesa and Antony Payton and Xiayi Ke and Whalley, {Lawrence J.} and Helen Fox and Paul Haggerty and William Ollier and Andrew Pickles and Porteous, {David J.} and Horan, {Michael A.} and Neil Pendleton and Starr, {John M.} and Deary, {Ian J.}",

year = "2012",

month = mar,

doi = "10.1038/ejhg.2011.201",

language = "English",

volume = "20",

pages = "341 -- 347",

journal = "European Journal of Human Genetics",

publisher = "Nature Publishing Group",

number = "3",

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Lopez, LM, Harris, SE, Luciano, M, Liewald, D, Davies, G, Gow, AJ, Tenesa, A, Payton, A, Ke, X, Whalley, LJ, Fox, H, Haggerty, P, Ollier, W, Pickles, A, Porteous, DJ, Horan, MA, Pendleton, N, Starr, JM & Deary, IJ 2012, 'Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts', European Journal of Human Genetics, vol. 20, no. 3, pp. 341 - 347. https://doi.org/10.1038/ejhg.2011.201

TY - JOUR

T1 - Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

AU - Lopez, Lorna M.

AU - Harris, Sarah E.

AU - Luciano, Michelle

AU - Liewald, Dave

AU - Davies, Gail

AU - Gow, Alan J.

AU - Tenesa, Albert

AU - Payton, Antony

AU - Ke, Xiayi

AU - Whalley, Lawrence J.

AU - Fox, Helen

AU - Haggerty, Paul

AU - Ollier, William

AU - Pickles, Andrew

AU - Porteous, David J.

AU - Horan, Michael A.

AU - Pendleton, Neil

AU - Starr, John M.

AU - Deary, Ian J.

PY - 2012/3

Y1 - 2012/3

N2 - Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. European Journal of Human Genetics (2012) 20, 341-347; doi:10.1038/ejhg.2011.201; published online 2 November 2011

AB - Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. European Journal of Human Genetics (2012) 20, 341-347; doi:10.1038/ejhg.2011.201; published online 2 November 2011

U2 - 10.1038/ejhg.2011.201

DO - 10.1038/ejhg.2011.201

M3 - Article

VL - 20

SP - 341

EP - 347

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 3

ER -

Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

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