Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Correction Volume: 10, Article Number: 2068 DOI: 10.1038/s41467-019-10160-w WOS:000466339700001General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P <5 x 10(-8)) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.Peer reviewe

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding Information: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Information networks among species:adaptations and counter-adaptations in acquiring and hiding information

Abstract Social information use is a widespread phenomenon across the animal kingdom and it affects various important aspects of animal behaviour. Animals observe and copy the behaviour of conspecifics and other species on the same trophic level in their own decision-making, e.g., in habitat or mate choice. Copying is adaptive only when it is selective. Thus, it would be important to understand when and which individuals should copy others, and which individuals they choose to copy and what are the consequences of social information use. In this thesis, I experimentally study these questions in wild animals living in natural conditions. By simulating arbitrary preference of great tits (Parus major), I demonstrated that the portrayed fitness does not affect the nest site choices of conspecifics, but the tit pairs with an old male prefer the nest site choices of good and poor conspecifics. Social information use among tits appears to be age- and sex-dependent. Pied flycatchers (Ficedula hypoleuca), however, selectively copy or reject a novel nest site feature preference (symbol attached to the nest box) of great tits experimentally manipulated to exhibit high or low fitness (clutch size), respectively. By offering pied flycatchers choice in nest boxes with alternative contents, I showed that nest take-overs of flycatchers are not a form of social information use, but seem to result from the reduced building effort required. Furthermore, by conducting a decoy and playback experiment, I showed that great tits covered eggs more efficiently in the presence of pied flycatchers. One function of egg covering behaviour seems to be a counter-adaptation to reduce information parasitism by pied flycatchers. My results demonstrate that the social transmission of behaviours across species can be highly selective in response to observed fitness, plausibly making the phenomenon adaptive. In contrast with the current theory of species coexistence, overlap between realized niches of species could dynamically increase or decrease, depending on the observed success of surrounding individuals. The social information revealed by success and behaviour of animals is a resource that can be used or concealed. It is a new kind of evolutionary and ecological factor which may affect the formation of ecosystems and species coevolution.Tiivistelmä Sosiaalinen informaationkäyttö on yleinen ilmiö eläinkunnassa, ja sitä tavataan aina hyönteisistä valaisiin. Yksilöt tarkkailevat ja kopioivat sekä lajitovereiden että toisen ekologialtaan samankaltaisen lajin yksilöiden käyttäytymistä erilaisissa tilanteissa, kuten pesäpaikan tai parittelukumppanin valinnassa. Sosiaalinen informaationkäyttö on adaptiivista ainoastaan ollessaan valikoivaa. Siksi on tärkeää selvittää kenen, koska ja ketä kannattaa kopioida, ja mitä ekologisia ja evolutiivisia seurauksia siitä koituu informaation lähteelle ja käyttäjälle. Väitöskirjassani tutkin kokeellisesti informaation hankkijan (kirjosieppo Ficedula hypoleuca) valikoivaa kopioimista ja siitä mahdollisesti johtuvaa informaation lähteen (talitiainen Parus major) vasta-adaptaatiota luonnonoloissa. Symbolikokeilla selvitin, että talitiaisten lajinsisäinen kopiointi on iästä ja sukupuolesta riippuvaa, mutta informaationlähteen havaittu kelpoisuus ei vaikuta kopioinnin todennäköisyyteen. Kirjosiepot puolestaan kopioivat valikoivasti keinotekoisesti luotuja tiaisten mieltymyksiä pesäpönttöön kiinnitettyjä symboleja kohtaan, riippuen tiaisten havaitusta manipuloidusta kelpoisuudesta (munamäärästä pesässä). Siepot kopioivat tiaisia, joiden pesässä on paljon munia (13 munaa), ja rejektoivat tiaisia (valitsevat vaihtoehtoisen symbolin), joilla munia on vähän (5 munaa). Tarjoamalla kirjosiepoille vaihtoehtoisia pesäpönttöjä osoitin, että sieppojen luontainen mieltymys vallata ja rakentaa pesänsä toisten pesien päälle ei ole sosiaalisen informaationkäytön muoto, vaan se näyttää olevan pesänrakennuksen kustannusten minimointia. Playback-kokeilla osoitin, että talitiaisten munienpeittelykäyttäytymisellä on useita funktioita. Se on vasta-adaptaatio kirjosiepon informaatioloisintaa vastaan ja toimii mahdollisesti suojana kylmää vastaan. Väitöskirjani tulokset osoittavat, että eläinten käyttäytymisen paljastama sosiaalinen informaatio on resurssi, jota voidaan hyödyntää tai salata. Se on myös uudenlainen ekologinen ja evolutiivinen tekijä, joka vaikuttaa eliöyhteisöjen muodostumiseen ja lajien koevoluutioon. Lajienvälinen valikoiva sosiaalinen informaationkäyttö -hypoteesi haastaa nykyisen koevoluutioteorian. Se ennustaa, että informaatiota hyödyntävän lajin ja informaationlähteen ominaisuudet voivat joko samankaltaistua tai erilaistua, informaationlähteen havaittavasta menestyksestä riippuen

Quantitative abilities of invertebrates:a methodological review

Abstract Quantitative abilities are widely recognized to play important roles in several ecological contexts, such as foraging, mate choice, and social interaction. Indeed, such abilities are widespread among vertebrates, in particular mammals, birds, and fish. Recently, there has been an increasing number of studies on the quantitative abilities of invertebrates. In this review, we present the current knowledge in this field, especially focusing on the ecological relevance of the capacity to process quantitative information, the similarities with vertebrates, and the different methods adopted to investigate this cognitive skill. The literature argues, beyond methodological differences, a substantial similarity between the quantitative abilities of invertebrates and those of vertebrates, supporting the idea that similar ecological pressures may determine the emergence of similar cognitive systems even in distantly related species

Oral exposure to thiacloprid-based pesticide (Calypso SC480) causes physical poisoning symptoms and impairs the cognitive abilities of bumble bees

Abstract Background: Pesticides are identified as one of the major reasons for the global pollinator decline. However, the sublethal effects of pesticide residue levels found in pollen and nectar on pollinators have been studied little. The aim of our research was to study whether oral exposure to the thiacloprid levels found in pollen and nectar affect the learning and long-term memory of bumble bees. We tested the effects of two exposure levels of thiacloprid-based pesticide (Calypso SC480) on buff-tailed bumble bee (Bombus terrestris) in laboratory utilizing a learning performance and memory tasks designed to be difficult enough to reveal large variations across the individuals. Results: The lower exposure level of the thiacloprid-based pesticide impaired the bees’ learning performance but not long-term memory compared to the untreated controls. The higher exposure level caused severe acute symptoms, due to which we were not able to test the learning and memory. Conclusions: Our results show that oral exposure to a thiacloprid-based pesticide, calculated based on residue levels found in pollen and nectar, not only causes sublethal effects but also acute lethal effects on bumble bees. Our study underlines an urgent demand for better understanding of pesticide residues in the environment, and of the effects of those residue levels on pollinators. These findings fill the gap in the existing knowledge and help the scientific community and policymakers to enhance the sustainable use of pesticides

Selective interspecific information use in the nest choice of solitary bees

Abstract Most of the studies on learning in bees have focused on the foraging context; we know little about the preferences and cognitive processes in nest-site selection, especially in solitary bees. The majority of the bee species are solitary and in contrast to eusocial bees, solitary bees’ cognition and social information use have remained largely unstudied. Solitary cavity-nesting mason bees (Osmia spp.) are an ideal system to study interspecific information use in nest choice in the wild as many species share similar nesting requirements. Here, we show that the blue mason bee (O. caerulescens) and the orange-vented mason bee (O. leaiana) examine hallmarks of parasitization of the nests of red mason bees (O. bicornis) before deciding where to establish their own nests. They were also presented with contextual cues (geometric symbols) that could be linked to parasitization by observational learning. Subjects subsequently had the choice of nesting in a nest site marked by the symbol that matched, or did not match, the one seen at the parasitized or healthy nest. We show that the bees copied and rejected the symbol of the examined nest manipulated to exhibit successful and unsuccessful nesting, respectively. We conclude that solitary bees use interspecific information in their nest-site selection. In contrast with current theories of species coexistence, niche overlap between species may dynamically change depending on the observed success of surrounding individuals