Abstract
General cognitive function is a prominent human trait associated with many important life outcomes1,2, including longevity3. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants4,5,6. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360; age range = 16 to 102). We found 9,714 genome-wide significant SNPs (P<5 x 10−8) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were SGCZ, ATXN1, MAPT, AUTS2, and P2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.
| Original language | English (US) |
|---|---|
| Journal | Unknown Journal |
| DOIs | |
| State | Published - Aug 17 2017 |
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- Immunology and Microbiology(all)
- Neuroscience(all)
- Pharmacology, Toxicology and Pharmaceutics(all)
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Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360). / Davies, Gail; Lam, Max; Harris, Sarah E.; Trampush, Joey W.; Luciano, Michelle; Hill, W. David; Hagenaars, Saskia P.; Ritchie, Stuart J.; Marioni, Riccardo E.; Fawns-Ritchie, Chloe; Liewald, David C.M.; Okely, Judith A.; Ahola-Olli, Ari V.; Barnes, Catriona L.K.; Bertram, Lars; Bis, Joshua C.; Burdick, Katherine E.; Christoforou, Andrea; DeRosse, Pamela; Djurovic, Srdjan; Espeseth, Thomas; Giakoumaki, Stella; Giddaluru, Sudheer; Gustavson, Daniel E.; Hayward, Caroline; Hofer, Edith; Ikram, M. Arfan; Karlsson, Robert; Knowles, Emma; Lahti, Jari; Leber, Markus; Li, Shuo; Mather, Karen A.; Melle, Ingrid; Morris, Derek; Oldmeadow, Christopher; Palviainen, Teemu; Payton, Antony; Pazoki, Raha; Petrovic, Katja; Reynolds, Chandra A.; Sargurupremraj, Muralidharan; Scholz, Markus; Smith, Jennifer A.; Smith, Albert V.; Terzikhan, Natalie; Thalamuthu, Anbu; Trompet, Stella; der Lee, Sven J.van; Ware, Erin B.; Windham, B. Gwen; Wright, Margaret J.; Yang, Jingyun; Yu, Jin; Ames, David; Amin, Najaf; Amouyel, Philippe; Andreassen, Ole A.; Armstrong, Nicola J.; Assareh, Amelia A.; Attia, John R.; Attix, Deborah; Avramopoulos, Dimitrios; Bennett, David A.; Böhmer, Anne C.; Boyle, Patricia A.; Brodaty, Henry; Campbell, Harry; Cannon, Tyrone D.; Cirulli, Elizabeth T.; Congdon, Eliza; Conley, Emily Drabant; Corley, Janie; Cox, Simon R.; Dale, Anders M.; Dehghan, Abbas; Dick, Danielle; Dickinson, Dwight; Eriksson, Johan G.; Evangelou, Evangelos; Faul, Jessica D.; Ford, Ian; Freimer, Nelson A.; Gao, He; Giegling, Ina; Gillespie, Nathan A.; Gordon, Scott D.; Gottesman, Rebecca F.; Griswold, Michael E.; Gudnason, Vilmundur; Harris, Tamara B.; Hartmann, Annette M.; Hatzimanolis, Alex; Heiss, Gerardo; Holliday, Elizabeth G.; Joshi, Peter K.; Kähönen, Mika; Kardia, Sharon L.R.; Karlsson, Ida; Kleineidam, Luca; Knopman, David S.; Kochan, Nicole A.; Konte, Bettina; Kwok, John B.; Hellard, Stephanie Le; Lee, Teresa; Lehtimäki, Terho; Li, Shu Chen; Liu, Tian; Koini, Marisa; London, Edythe; Longstreth, Will T.; Lopez, Oscar L.; Loukola, Anu; Luck, Tobias; Lundervold, Astri J.; Lundquist, Anders; Lyytikäinen, Leo Pekka; Martin, Nicholas G.; Montgomery, Grant W.; Murray, Alison D.; Need, Anna C.; Noordam, Raymond; Nyberg, Lars; Ollier, William; Papenberg, Goran; Pattie, Alison; Polasek, Ozren; Poldrack, Russell A.; Psaty, Bruce M.; Reppermund, Simone; Riedel-Heller, Steffi G.; Rose, Richard J.; Rotter, Jerome I.; Roussos, Panos; Rovio, Suvi P.; Saba, Yasaman; Sabb, Fred W.; Sachdev, Perminder S.; Satizabal, Claudia; Schmid, Matthias; Scott, Rodney J.; Scult, Matthew A.; Simino, Jeannette; Slagboom, P. Eline; Smyrnis, Nikolaos; Soumaré, Aïcha; Stefanis, Nikos C.; Stott, David J.; Straub, Richard E.; Sundet, Kjetil; Taylor, Adele M.; Taylor, Kent D.; Tzoulaki, Ioanna; Tzourio, Christophe; Uitterlinden, André; Vitart, Veronique; Voineskos, Aristotle N.; Kaprio, Jaakko; Wagner, Michael; Wagner, Holger; Weinhold, Leonie; Wen, K. Hoyan; Widen, Elisabeth; Yang, Qiong; Zhao, Wei; Adams, Hieab H.H.; Arking, Dan E.; Bilder, Robert M.; Bitsios, Panos; Boerwinkle, Eric; Chiba-Falek, Ornit; Corvin, Aiden; Jager, Philip L.De; Debette, Stéphanie; Donohoe, Gary; Elliott, Paul; Fitzpatrick, Annette L.; Gill, Michael; Glahn, David C.; Hägg, Sara; Hansell, Narelle K.; Hariri, Ahmad R.; Ikram, M. Kamran; Jukema, J. Wouter; Vuoksimaa, Eero; Keller, Matthew C.; Kremen, William S.; Launer, Lenore; Lindenberger, Ulman; Palotie, Aarno; Pedersen, Nancy L.; Pendleton, Neil; Porteous, David J.; Räikkönen, Katri; Raitakari, Olli T.; Ramirez, Alfredo; Reinvang, Ivar; Rudan, Igor; Rujescu, Dan; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter W.; Schofield, Peter R.; Starr, John M.; Steen, Vidar M.; Trollor, Julian N.; Turner, Steven T.; Duijn, Cornelia M.Van; Villringer, Arno; Weinberger, Daniel R.; Weir, David R.; Wilson, James F.; Malhotra, Anil; McIntosh, Andrew M.; Gale, Catharine R.; Seshadri, Sudha; Mosley, Thomas H.; Bressler, Jan; Lencz, Todd; Deary, Ian J.
In: Unknown Journal, 17.08.2017.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)
AU - Davies, Gail
AU - Lam, Max
AU - Harris, Sarah E.
AU - Trampush, Joey W.
AU - Luciano, Michelle
AU - Hill, W. David
AU - Hagenaars, Saskia P.
AU - Ritchie, Stuart J.
AU - Marioni, Riccardo E.
AU - Fawns-Ritchie, Chloe
AU - Liewald, David C.M.
AU - Okely, Judith A.
AU - Ahola-Olli, Ari V.
AU - Barnes, Catriona L.K.
AU - Bertram, Lars
AU - Bis, Joshua C.
AU - Burdick, Katherine E.
AU - Christoforou, Andrea
AU - DeRosse, Pamela
AU - Djurovic, Srdjan
AU - Espeseth, Thomas
AU - Giakoumaki, Stella
AU - Giddaluru, Sudheer
AU - Gustavson, Daniel E.
AU - Hayward, Caroline
AU - Hofer, Edith
AU - Ikram, M. Arfan
AU - Karlsson, Robert
AU - Knowles, Emma
AU - Lahti, Jari
AU - Leber, Markus
AU - Li, Shuo
AU - Mather, Karen A.
AU - Melle, Ingrid
AU - Morris, Derek
AU - Oldmeadow, Christopher
AU - Palviainen, Teemu
AU - Payton, Antony
AU - Pazoki, Raha
AU - Petrovic, Katja
AU - Reynolds, Chandra A.
AU - Sargurupremraj, Muralidharan
AU - Scholz, Markus
AU - Smith, Jennifer A.
AU - Smith, Albert V.
AU - Terzikhan, Natalie
AU - Thalamuthu, Anbu
AU - Trompet, Stella
AU - der Lee, Sven J.van
AU - Ware, Erin B.
AU - Windham, B. Gwen
AU - Wright, Margaret J.
AU - Yang, Jingyun
AU - Yu, Jin
AU - Ames, David
AU - Amin, Najaf
AU - Amouyel, Philippe
AU - Andreassen, Ole A.
AU - Armstrong, Nicola J.
AU - Assareh, Amelia A.
AU - Attia, John R.
AU - Attix, Deborah
AU - Avramopoulos, Dimitrios
AU - Bennett, David A.
AU - Böhmer, Anne C.
AU - Boyle, Patricia A.
AU - Brodaty, Henry
AU - Campbell, Harry
AU - Cannon, Tyrone D.
AU - Cirulli, Elizabeth T.
AU - Congdon, Eliza
AU - Conley, Emily Drabant
AU - Corley, Janie
AU - Cox, Simon R.
AU - Dale, Anders M.
AU - Dehghan, Abbas
AU - Dick, Danielle
AU - Dickinson, Dwight
AU - Eriksson, Johan G.
AU - Evangelou, Evangelos
AU - Faul, Jessica D.
AU - Ford, Ian
AU - Freimer, Nelson A.
AU - Gao, He
AU - Giegling, Ina
AU - Gillespie, Nathan A.
AU - Gordon, Scott D.
AU - Gottesman, Rebecca F.
AU - Griswold, Michael E.
AU - Gudnason, Vilmundur
AU - Harris, Tamara B.
AU - Hartmann, Annette M.
AU - Hatzimanolis, Alex
AU - Heiss, Gerardo
AU - Holliday, Elizabeth G.
AU - Joshi, Peter K.
AU - Kähönen, Mika
AU - Kardia, Sharon L.R.
AU - Karlsson, Ida
AU - Kleineidam, Luca
AU - Knopman, David S.
AU - Kochan, Nicole A.
AU - Konte, Bettina
AU - Kwok, John B.
AU - Hellard, Stephanie Le
AU - Lee, Teresa
AU - Lehtimäki, Terho
AU - Li, Shu Chen
AU - Liu, Tian
AU - Koini, Marisa
AU - London, Edythe
AU - Longstreth, Will T.
AU - Lopez, Oscar L.
AU - Loukola, Anu
AU - Luck, Tobias
AU - Lundervold, Astri J.
AU - Lundquist, Anders
AU - Lyytikäinen, Leo Pekka
AU - Martin, Nicholas G.
AU - Montgomery, Grant W.
AU - Murray, Alison D.
AU - Need, Anna C.
AU - Noordam, Raymond
AU - Nyberg, Lars
AU - Ollier, William
AU - Papenberg, Goran
AU - Pattie, Alison
AU - Polasek, Ozren
AU - Poldrack, Russell A.
AU - Psaty, Bruce M.
AU - Reppermund, Simone
AU - Riedel-Heller, Steffi G.
AU - Rose, Richard J.
AU - Rotter, Jerome I.
AU - Roussos, Panos
AU - Rovio, Suvi P.
AU - Saba, Yasaman
AU - Sabb, Fred W.
AU - Sachdev, Perminder S.
AU - Satizabal, Claudia
AU - Schmid, Matthias
AU - Scott, Rodney J.
AU - Scult, Matthew A.
AU - Simino, Jeannette
AU - Slagboom, P. Eline
AU - Smyrnis, Nikolaos
AU - Soumaré, Aïcha
AU - Stefanis, Nikos C.
AU - Stott, David J.
AU - Straub, Richard E.
AU - Sundet, Kjetil
AU - Taylor, Adele M.
AU - Taylor, Kent D.
AU - Tzoulaki, Ioanna
AU - Tzourio, Christophe
AU - Uitterlinden, André
AU - Vitart, Veronique
AU - Voineskos, Aristotle N.
AU - Kaprio, Jaakko
AU - Wagner, Michael
AU - Wagner, Holger
AU - Weinhold, Leonie
AU - Wen, K. Hoyan
AU - Widen, Elisabeth
AU - Yang, Qiong
AU - Zhao, Wei
AU - Adams, Hieab H.H.
AU - Arking, Dan E.
AU - Bilder, Robert M.
AU - Bitsios, Panos
AU - Boerwinkle, Eric
AU - Chiba-Falek, Ornit
AU - Corvin, Aiden
AU - Jager, Philip L.De
AU - Debette, Stéphanie
AU - Donohoe, Gary
AU - Elliott, Paul
AU - Fitzpatrick, Annette L.
AU - Gill, Michael
AU - Glahn, David C.
AU - Hägg, Sara
AU - Hansell, Narelle K.
AU - Hariri, Ahmad R.
AU - Ikram, M. Kamran
AU - Jukema, J. Wouter
AU - Vuoksimaa, Eero
AU - Keller, Matthew C.
AU - Kremen, William S.
AU - Launer, Lenore
AU - Lindenberger, Ulman
AU - Palotie, Aarno
AU - Pedersen, Nancy L.
AU - Pendleton, Neil
AU - Porteous, David J.
AU - Räikkönen, Katri
AU - Raitakari, Olli T.
AU - Ramirez, Alfredo
AU - Reinvang, Ivar
AU - Rudan, Igor
AU - Rujescu, Dan
AU - Schmidt, Reinhold
AU - Schmidt, Helena
AU - Schofield, Peter W.
AU - Schofield, Peter R.
AU - Starr, John M.
AU - Steen, Vidar M.
AU - Trollor, Julian N.
AU - Turner, Steven T.
AU - Duijn, Cornelia M.Van
AU - Villringer, Arno
AU - Weinberger, Daniel R.
AU - Weir, David R.
AU - Wilson, James F.
AU - Malhotra, Anil
AU - McIntosh, Andrew M.
AU - Gale, Catharine R.
AU - Seshadri, Sudha
AU - Mosley, Thomas H.
AU - Bressler, Jan
AU - Lencz, Todd
AU - Deary, Ian J.
N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2017/8/17
Y1 - 2017/8/17
N2 - General cognitive function is a prominent human trait associated with many important life outcomes1,2, including longevity3. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants4,5,6. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360; age range = 16 to 102). We found 9,714 genome-wide significant SNPs (P<5 x 10−8) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were SGCZ, ATXN1, MAPT, AUTS2, and P2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.
AB - General cognitive function is a prominent human trait associated with many important life outcomes1,2, including longevity3. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants4,5,6. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360; age range = 16 to 102). We found 9,714 genome-wide significant SNPs (P<5 x 10−8) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were SGCZ, ATXN1, MAPT, AUTS2, and P2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.
UR - http://www.scopus.com/inward/record.url?scp=85095637577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095637577&partnerID=8YFLogxK
U2 - 10.1101/176511
DO - 10.1101/176511
M3 - Article
AN - SCOPUS:85095637577
JO - Advances in Water Resources
JF - Advances in Water Resources
SN - 0309-1708
ER -