A functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly

Zoltán Bochdanovits; Florencia M. Gosso; Linda Van Den Berg; Patrizia Rizzu; Tinca J.C. Polderman; Luba M. Pardo; Lorna M. Houlihan; Michelle Luciano; John M. Starr; Sarah E. Harris; Ian J. Deary; Eco J.C. De Geus; Dorret I. Boomsma; Peter Heutink; Danielle Posthuma

doi:10.1007/s10519-008-9233-0

A functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly

Zoltán Bochdanovits^*, Florencia M. Gosso, Linda Van Den Berg, Patrizia Rizzu, Tinca J.C. Polderman, Luba M. Pardo, Lorna M. Houlihan, Michelle Luciano, John M. Starr, Sarah E. Harris, Ian J. Deary, Eco J.C. De Geus, Dorret I. Boomsma, Peter Heutink, Danielle Posthuma

^*Corresponding author for this work

Dermatology

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

18 Citations (Scopus)

Abstract

Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and chimpanzee. Positively selected genes among primates are generally presumed to determine phenotypic differences between humans and chimpanzee, such as the enhanced cognitive ability of our species. Amino acid substitutions segregating in humans at positively selected amino acid sites are expected to affect phenotypic differences among humans. Therefore we conducted an association study in two family based cohorts and one population based cohort between cognitive ability and the most likely candidate gene among the five that harbored more than one such polymorphism. The derived, human-specific allele of the beta-2 adrenergic receptor Arg16Gly polymorphism was found to be the increaser allele for performance IQ in the young, family based cohort but the decreaser allele for two different measures of cognition in the large Scottish cohort of unrelated individuals. The polymorphism is known to affect signaling activity and modulation of beta-2 adrenergic signaling has been shown to adjust memory consolidation, a trait related to cognition. The opposite effect of the polymorphism on cognition in the two age classes observed in the different cohorts resembles the effect of ADRB2 on hypertension, which also has been reported to be age dependent. This result illustrates the relevance of comparative genomics to detect genes that are involved in human behavior.

Original language	English
Pages (from-to)	15-23
Number of pages	9
Journal	Behavior Genetics
Volume	39
Early online date	15 Oct 2008
DOIs	https://doi.org/10.1007/s10519-008-9233-0
Publication status	Published - Jan 2009

Bibliographical note

We would also like to thank the families from the Netherland Twin Registry (NTR) who participated in this study. We thank the LBC1936 cohort members. We thank the study secretary Paula Davies. We thank Janie Corley, Caroline Brett and Caroline Cameron for data collection and data entry. We thank the nurses and staff at the WT-CRF where the data was collected. We thank the staff at the Lothian Health Broad, and the staff at the SCRE Centre, University of Glasgow.

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Bochdanovits, Z., Gosso, F. M., Van Den Berg, L., Rizzu, P., Polderman, T. J. C., Pardo, L. M., Houlihan, L. M., Luciano, M., Starr, J. M., Harris, S. E., Deary, I. J., De Geus, E. J. C., Boomsma, D. I., Heutink, P., & Posthuma, D. (2009). A functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly. Behavior Genetics, 39, 15-23. https://doi.org/10.1007/s10519-008-9233-0

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title = "A functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly",

abstract = "Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and chimpanzee. Positively selected genes among primates are generally presumed to determine phenotypic differences between humans and chimpanzee, such as the enhanced cognitive ability of our species. Amino acid substitutions segregating in humans at positively selected amino acid sites are expected to affect phenotypic differences among humans. Therefore we conducted an association study in two family based cohorts and one population based cohort between cognitive ability and the most likely candidate gene among the five that harbored more than one such polymorphism. The derived, human-specific allele of the beta-2 adrenergic receptor Arg16Gly polymorphism was found to be the increaser allele for performance IQ in the young, family based cohort but the decreaser allele for two different measures of cognition in the large Scottish cohort of unrelated individuals. The polymorphism is known to affect signaling activity and modulation of beta-2 adrenergic signaling has been shown to adjust memory consolidation, a trait related to cognition. The opposite effect of the polymorphism on cognition in the two age classes observed in the different cohorts resembles the effect of ADRB2 on hypertension, which also has been reported to be age dependent. This result illustrates the relevance of comparative genomics to detect genes that are involved in human behavior.",

author = "Zolt{\'a}n Bochdanovits and Gosso, {Florencia M.} and {Van Den Berg}, Linda and Patrizia Rizzu and Polderman, {Tinca J.C.} and Pardo, {Luba M.} and Houlihan, {Lorna M.} and Michelle Luciano and Starr, {John M.} and Harris, {Sarah E.} and Deary, {Ian J.} and {De Geus}, {Eco J.C.} and Boomsma, {Dorret I.} and Peter Heutink and Danielle Posthuma",

note = "We would also like to thank the families from the Netherland Twin Registry (NTR) who participated in this study. We thank the LBC1936 cohort members. We thank the study secretary Paula Davies. We thank Janie Corley, Caroline Brett and Caroline Cameron for data collection and data entry. We thank the nurses and staff at the WT-CRF where the data was collected. We thank the staff at the Lothian Health Broad, and the staff at the SCRE Centre, University of Glasgow.",

year = "2009",

month = jan,

doi = "10.1007/s10519-008-9233-0",

language = "English",

volume = "39",

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journal = "Behavior Genetics",

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Bochdanovits, Z, Gosso, FM, Van Den Berg, L, Rizzu, P, Polderman, TJC, Pardo, LM, Houlihan, LM, Luciano, M, Starr, JM, Harris, SE, Deary, IJ, De Geus, EJC, Boomsma, DI, Heutink, P & Posthuma, D 2009, 'A functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly', Behavior Genetics, vol. 39, pp. 15-23. https://doi.org/10.1007/s10519-008-9233-0

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AU - Bochdanovits, Zoltán

AU - Gosso, Florencia M.

AU - Van Den Berg, Linda

AU - Rizzu, Patrizia

AU - Polderman, Tinca J.C.

AU - Pardo, Luba M.

AU - Houlihan, Lorna M.

AU - Luciano, Michelle

AU - Starr, John M.

AU - Harris, Sarah E.

AU - Deary, Ian J.

AU - De Geus, Eco J.C.

AU - Boomsma, Dorret I.

AU - Heutink, Peter

AU - Posthuma, Danielle

N1 - We would also like to thank the families from the Netherland Twin Registry (NTR) who participated in this study. We thank the LBC1936 cohort members. We thank the study secretary Paula Davies. We thank Janie Corley, Caroline Brett and Caroline Cameron for data collection and data entry. We thank the nurses and staff at the WT-CRF where the data was collected. We thank the staff at the Lothian Health Broad, and the staff at the SCRE Centre, University of Glasgow.

PY - 2009/1

Y1 - 2009/1

N2 - Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and chimpanzee. Positively selected genes among primates are generally presumed to determine phenotypic differences between humans and chimpanzee, such as the enhanced cognitive ability of our species. Amino acid substitutions segregating in humans at positively selected amino acid sites are expected to affect phenotypic differences among humans. Therefore we conducted an association study in two family based cohorts and one population based cohort between cognitive ability and the most likely candidate gene among the five that harbored more than one such polymorphism. The derived, human-specific allele of the beta-2 adrenergic receptor Arg16Gly polymorphism was found to be the increaser allele for performance IQ in the young, family based cohort but the decreaser allele for two different measures of cognition in the large Scottish cohort of unrelated individuals. The polymorphism is known to affect signaling activity and modulation of beta-2 adrenergic signaling has been shown to adjust memory consolidation, a trait related to cognition. The opposite effect of the polymorphism on cognition in the two age classes observed in the different cohorts resembles the effect of ADRB2 on hypertension, which also has been reported to be age dependent. This result illustrates the relevance of comparative genomics to detect genes that are involved in human behavior.

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A functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly

Abstract

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