A Functional Polymorphism under Positive Evolutionary Selection in ADRB2 is Associated with Human Intelligence with Opposite Effects in the Young and the Elderly |
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Authors: | 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 |
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Institution: | Department of Clinical Genetics, Section of Medical Genomics, VU Medical Center, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. z.bochdanovits@vumc.nl |
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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.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Edited by Tatiana Foroud. |
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Keywords: | Comparative genomics Human evolution IQ Genetic association Functional polymorphism |
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