7 research outputs found
Формирование эмоциональной культуры как компонента инновационной культуры студентов
- Author
- A Abdellaoui
- A Garrod
- A Wright
- Abdel Abdellaoui
- Adesola Ogunniyi
- Adolfo Correa
- Alan F. Wright
- Alan R. Shuldiner
- Alanna Morrison
- Albert V. Smith
- Albertine J. Oldehinkel
- Alena Stančáková
- Alexander Drong
- Alexander Teumer
- Alice V. Stanton
- Aliki-Eleni Farmaki
- Amelie Bonnefond
- Anders Hamsten
- Andre G. Uitterlinden
- Andres Metspalu
- Andrew A. Hicks
- Andrew Bjonnes
- Andrew D. Morris
- Andrew P. Morris
- Andrew R. Wood
- Angela Matchan
- Anil K. Giri
- Anke Tönjes
- Anna Maria Töglhofer
- Annamari Lundqvist
- Anne U. Jackson
- Anni Joensuu
- Antonietta Robino
- Antti-Pekka Sarin
- Anu Loukola
- AR Wood
- Aravinda Chakravarti
- Archie Campbell
- Ashley van der Spek
- Astrid van Hylckama Vlieg
- Atsushi Takahashi
- Babatunde Salako
- Bamidele O. Tayo
- Bengt Sennblad
- Benjamin Lehne
- Beverley Balkau
- Bjarke Feenstra
- Blair H. Smith
- Bruce M. Psaty
- C Darwin
- C Darwin
- CA Rietveld
- Carole Ober
- Caroline Hayward
- Caroline S. Fox
- Cecilia M. Lindgren
- Charles Gu
- Charles N. Rotimi
- Chittaranjan S. Yajnik
- Chris Haley
- Christa Meisinger
- Christian Gieger
- Christopher J. Hammond
- Cinzia Sala
- CJ Willer
- Claude Bouchard
- Claudia Schurmann
- Clemens Baumbach
- Colin N. A. Palmer
- Constance Chen
- Cornelia M. van Duijn
- Cornelius A. Rietveld
- Corrado Masciullo
- Cristian Pattaro
- Cristina Menni
- D Charlesworth
- Daniel I. Chasman
- Daniel J. Benjamin
- Daniel Shriner
- Daniela Ruggiero
- Daniela Toniolo
- Daniele Cusi
- David A. Mackey
- David C.M. Liewald
- David J. Porteous
- David P. Strachan
- David R. Weir
- Degui Zhi
- Dhananjay Vaidya
- Dharambir K. Sanghera
- Diane M. Becker
- Diego Vozzi
- Donna K. Arnett
- Dorret I. Boomsma
- Dragana Vuckovic
- Dwaipayan Bharadwaj
- Edith Hofer
- Eero Vuoksimaa
- Efthymia Vlachopoulou
- Eleftheria Zeggini
- Eric Boerwinkle
- Erik Ingelsson
- Erika Salvi
- Erin B. Ware
- Erkki Vartiainen
- Erwin P. Bottinger
- Evelin Mihailov
- F Galton
- Folkert W. Asselbergs
- Francesca Pavani
- Francine Grodstein
- Francis S. Collins
- Frank D. Mentch
- Frank Geller
- Gail Davies
- GB Ehret
- Generation Scotland
- Georg Ehret
- Georg Homuth
- George Davey Smith
- George Dedoussis
- George T. O'Connor
- Gerard Pasterkamp
- Gianluigi Zaza
- Gibran Hemani
- Giorgia Girotto
- Giovanni Gambaro
- Giovanni Malerba
- Giriraj R. Chandak
- Gonneke Willemsen
- Grant W. Montgomery
- H Campbell
- H Lango Allen
- H Najmabadi
- H Stefansson
- Hakon Hakonarson
- Hannele Mattsson
- Hans Bisgaard
- Hao Mei
- Harri Rissanen
- Harry Campbell
- Heikki A. Koistinen
- Helen R. Warren
- Helena Schmidt
- Henning Tiemeier
- Hugoline G. de Haan
- I Rudan
- Ian Ford
- Ian J. Deary
- Igor Rudan
- IJ Deary
- Ilaria Gandin
- Ilja Demuth
- Ilja M. Nolte
- Inga Patarcic
- Inga Prokopenko
- Ingrid B. Borecki
- Irina Gillham-Nasenya
- J Gibson
- J. Wouter Jukema
- Jaakko Kaprio
- Jaakko Tuomilehto
- James B. Meigs
- James F. Wilson
- James G. Wilson
- James S. Pankow
- Jari Lahti
- Jaspal S. Kooner
- JE Powell
- Jeffrey R. O'Connel
- Jennifer A. Smith
- Jennifer E. Huffman
- Jerome I. Rotter
- Jessica D. Faul
- Jessica van Setten
- JI Hoffman
- Jie Yao
- Jing Hua Zhao
- Jinyan Huang
- Joel N. Hirschhorn
- Johan G. Eriksson
- Johanna Kuusisto
- John B. Whitfield
- John C. Chambers
- John Connell
- John M. Starr
- John R. B. Perry
- Jonathan P. Bradfield
- Josée Dupuis
- Jouke-Jan Hottenga
- JR Flynn
- Juha Sinisalo
- JV Neel
- Karen L. Mohlke
- Kari E. North
- Kauko Heikkilä
- Kent D. Taylor
- Kirsi Pietilainen
- Koichi Matsuda
- Konstantin Strauch
- KW Broman
- L Ronnegard
- L. Adrienne Cupples
- LA Weiss
- Lars Bertram
- Lars Lind
- Laura J. Scott
- Lawrence F. Bielak
- Lazaros Lataniotis
- Leanne M. Hall
- Lenore J. Launer
- Lihua Wang
- Lili Milani
- Lisa R. Yanek
- Lisbeth Carstensen
- Loic Yengo
- Lorraine Southam
- Louis Pérusse
- Luigi Ferrucci
- LV Hedges
- Lyn R. Griffiths
- Lynda M. Rose
- Lynne J. Hocking
- M Kirin
- M Soler Artigas
- M. Arfan Ikram
- MA Nalls
- Maciej Tomaszewski
- Mads Melbye
- Magnus Johannesson
- Manraj K. Kooner
- Marcus Dörr
- Margie J. Wright
- Mari Nelis
- Maria G. Stathopoulou
- Maria Pina Concas
- Marie Loh
- Marilyn C. Cornelis
- Marina Ciullo
- Mario Pirastu
- Marja-Liisa Lokki
- Mark Abney
- Mark J. Caulfield
- Markku Laakso
- Markku S. Nieminen
- Markus Perola
- Mary F. Feitosa
- Massimo Mangino
- Matthew A. Allison
- Matthew J. Suderman
- May E. Montasser
- MC Keller
- MC Keller
- Melanie Waldenberger
- Michael Boehnke
- Michela Traglia
- Michiaki Kubo
- Mika Kähönen
- Miles C. Benton
- Misa Graff
- Najaf Amin
- Nancy L. Heard-Costa
- Natalia Tšernikova
- Naveed Sattar
- Nazir M. Khan
- NE Morton
- Neil Poulter
- Nele Friedrich
- Nicholas D. Hastie
- Nicholas G. Martin
- Nicholas J. Timpson
- Nicholas J. Wareham
- Nicola Pirastu
- Nicole Soranzo
- Niek Verweij
- Niina Eklund
- Nikhil Tandon
- Nilesh J. Samani
- Nona Sotoodehnia
- Nora Franceschini
- Olga McLeod
- Olli Raitakari
- Omri Gottesman
- Ozren Polašek
- Panos Deloukas
- Paolo Gasparini
- Patricia A. Peyser
- Patricia B. Munroe
- Patrik K. E. Magnusson
- Pau Navarro
- Paul Knekt
- Paul M. Ridker
- Paul Redmond
- Pedro Marques-Vidal
- Pekka Jousilahti
- Penelope A. Lind
- Peter J. van der Most
- Peter K. Joshi
- Peter Kraft
- Peter Sever
- Peter Vollenweider
- Philipp Koellinger
- Philippe Froguel
- Pim van der Harst
- Pirro G. Hysi
- R McQuillan
- R McQuillan
- R. Graham Barr
- RA Scott
- Rajiv Nadukuru
- Rany M. Salem
- Rasika A. Mathias
- RE Marioni
- RE Marioni
- Reedik Mägi
- Reinhold Schmidt
- Richa Saxena
- Richard H. Myers
- Richard Rose
- Richard S. Cooper
- Robert A. Scott
- Rodney A. Lea
- Rona J. Strawbridge
- Ruth J. F. Loos
- S Purcell
- S Wright
- S Wright
- Sailaja Vedantam
- Saira S. Mirza
- Sander W. van der Laan
- Sandosh Padmanabhan
- Sarah E. Harris
- Sarah E. Medland
- Sarah Wild
- Sarju Ralhan
- Satu Männistö
- Sebastian E. Baumeister
- Seyhan Yazar
- Sharon L. R. Kardia
- Sheila Ulivi
- Shona M. Kerr
- Sian-Tsun Tang
- Smeeta Shrestha
- Sonja I. Berndt
- Stavroula Kanoni
- Stefan Enroth
- Stefania Cappellani
- Stella Trompet
- Stephan J. L. Bakker
- Stephanie J. London
- Stephanie J. Loomis
- Stephen B. Ellis
- Stephen J. Chanock
- Stephen S. Rich
- Steven C. Hunt
- Struan F.A. Grant
- Sudha Seshadri
- Suraj S. Nongmaithem
- Sven Bergmann
- Tamara B. Harris
- Tanguy Corre
- Tarunveer S. Ahluwalia
- Teresa Nutile
- Terho Lehtimäki
- Thomas Lumley
- Thomas Meitinger
- Thorkild I. A. Sørensen
- Tian Liu
- Tim D. Spector
- Tim Kacprowski
- Timothy M. Frayling
- TJ Pemberton
- Tonu Esko
- Traci M. Bartz
- Tugce Karaderi
- Tuula Vasankari
- Ulf Gyllensten
- Ulman Lindenberger
- Ulrich Broeckel
- Uzma Afzal
- Veikko Salomaa
- Veronique Vitart
- Vilmundur Gudnason
- Walter R. Palmas
- Wei Zhao
- Weihua Meng
- Weihua Zhang
- William R. Scott
- William Wentworth-Shields
- Xiaofeng Zhu
- Xiuqing Guo
- Y.-D. Ida Chen
- Ying Wu
- Yingchang Lu
- Yingleong Chan
- Yoichiro Kamatani
- YS Aulchenko
- YS Aulchenko
- Yukinori Okada
- Yuning Chen
- Zhaoming Wang
- Åsa Johansson
- Publication venue
- Российский государственный профессионально-педагогический университет
- Publication date
- 01/01/2009
- Field of study
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
Phenome-wide association studies across large population cohorts support drug target validation
- Author
- Alanne-Kinnunen Mervi
- Bhandari Aman
- Bing Nan
- Chatterjee Arnaub K.
- Daly Mark J.
- Day-Williams Aaron G.
- Diogo Dorothee
- Donnelly Peter
- Estrada Karol
- Fox Caroline S.
- Franklin Christopher S.
- Hakonarson Hakon
- Hinds David A.
- Hutz Janna
- John Sally
- Kilpelainen Elina
- Macarthur Daniel G.
- Maranville Joseph C.
- March Michael
- Mattsson Hannele
- McElwee Joshua
- Nguyen Khanh-Dung H.
- Palotie Aarno
- Plenge Robert M.
- Reeve Mary-Pat
- Reilly Dermot F.
- Ripatti Samuli
- Runz Heiko
- Salomaa Veikko
- Sleiman Patrick M. A.
- Spencer Chris C. A.
- Tian Chao
- Vangjeli Ciara
- Weale Michael E.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Recommended from our members
Associations of autozygosity with a broad range of human phenotypes
- Author
- Adeyemo Adebowale A
- Afaq Saima
- Aguilar-Salinas Carlos Alberto
- Akiyama Masato
- Albert Matthew L
- Allison Matthew A
- Alver Maris
- Amin Najaf
- Asselbergs Folkert W
- Aung Tin
- Azizi Fereidoun
- Bakker Stephan J L
- Bao Yanchun
- Barnes Catriona L K
- Bartz Traci M
- Baumbach Clemens
- Becker Diane M
- Bennett David A
- Bentley Amy R
- Berndt Sonja I
- Bharadwaj Dwaipayan
- Bielak Lawrence F
- Biino Ginevra
- Bixley Matthew J
- Bochud Murielle
- Boehnke Mike
- Boeing Heiner
- Boerwinkle Eric
- Borja Judith B
- Bottinger Erwin P
- Bouchard Claude
- Bradfield Jonathan P
- Brody Jennifer A
- Broer Linda
- Brumat Marco
- Campbell Archie
- Campbell Harry
- Carmi Shai
- Caulfield Mark J
- Cesarini David
- Chai Jin-Fang
- Chambers John C
- Chandak Giriraj Ratan
- Chanock Stephen
- Chasman Daniel I
- Chee Miao-Li
- Chen Guanjie
- Chen Yii-Der I
- Chen Zhengming
- Cheng Ching-Yu
- Chiu Yen-Feng
- Ciullo Marina
- Clark David W
- Cocca Massimiliano
- Collins Francis S
- Concas Maria Pina
- Corley Janie
- Cornelis Marilyn
- Corre Tanguy
- Cousminer Diana L
- Cugliari Giovanni
- Cusi Daniele
- Damulina Anna
- Daneshpour Maryam S
- Day Felix R
- de Borst Gert J
- de Haan Hugoline G
- De Jager Philip L
- de Kleijn Dominique P V
- de Mutsert Renée
- Deary Ian J
- Deelen Patrick
- Dekker Annelot M
- Delgado Graciela E
- Den Ruijter Hester M
- Dhana Klodian
- Doney Alexander S F
- Dorajoo Rajkumar
- Doumatey Ayo P
- Dzimiri Nduna
- Dörr Marcus
- Ebenesersdóttir S Sunna
- Eccles David A
- Ellinghaus David
- Elliott Joshua
- Elliott Paul
- Erdmann Jeanette
- Eriksson Johan G
- Esko Tōnu
- Evangelou Evangelos
- Evans Michele K
- Ewert Ralf
- Faul Jessica D
- Feenstra Bjarke
- Feitosa Mary
- Felix Janine F
- Fischer Krista
- Foisy Sylvain
- Franceschini Nora
- Franke Andre
- Franke Lude
- Freedman Barry I
- Friedlander Yechiel
- Fuchsberger Christian
- Gandin Ilaria
- Gao He
- Gasparini Paolo
- Germain Marine
- Gieger Christian
- Girotto Giorgia
- Giulianini Franco
- Goel Anuj
- Gonzalez Clicerio
- Goodarzi Mark O
- Gordon Scott D
- Goyette Philippe
- Graff Mariaelisa
- Granot-Hershkovitz Einat
- Grant Struan F A
- Griffiths Lyn R
- Grodstein Francine
- Groop Leif
- Guarrera Simonetta
- Gudbjartsson Daniel F
- Gudnason Vilmundur
- Guity Kamran
- Gunnarsson Bjarni
- Guo Xiuqing
- Guo Yu
- Gyllensten Ulf
- Gögele Martin
- Hagenaars Saskia P
- Haiman Christopher A
- Hakonarson Hakon
- Halevy Avner
- Haley Chris S
- Hamsten Anders
- Harris Sarah E
- Harris Tamara B
- Hayward Caroline
- Hedayati Mehdi
- Helgason Agnar
- Heng Chew-Kiat
- Hicks Andrew A
- Hirata Makoto
- Hochner Hagit
- Hofer Edith
- Hsiung Chao Agnes
- Huang Jinyan
- Huerta-Chagoya Alicia
- Huikuri Heikki
- Hung Yi-Jen
- Hunt Steven C
- Höfer Imo
- Igartua Catherine
- Ikram M Arfan
- Jaddoe Vincent W V
- Jagadeesan Anuradha
- Jansen Iris E
- Jia Yucheng
- Johannesson Magnus
- Johansson Åsa
- Jonas Jost B
- Joshi Peter K
- Jousilahti Pekka
- Jukema J Wouter
- Junttila Juhani
- Kacprowski Tim
- Kamatani Yoichiro
- Kanai Masahiro
- Kaprio Jaakko
- Kardia Sharon L. R.
- Karlsson Robert
- Karlsson Torgny
- Karpe Fredrik
- Kerrison Nicola D
- Kessler Thorsten
- Khaw Kay-Tee
- Khor Chiea Chuen
- Kleber Marcus E
- Koh Woon-Puay
- Kolcic Ivana
- Kooner Jaspal S
- Kraft Peter
- Krämer Bernhard K
- Kubo Michiaki
- Kumari Meena
- Kutalik Zoltán
- Kuusisto Johanna
- Laakso Markku
- Lahti Jari
- Langenberg Claudia
- Laudes Matthias
- Launer Lenore J
- Lawlor Deborah A
- Lea Rodney A
- Lee I-Te
- Lee Wen-Jane
- Lehne Benjamin
- Lerch Markus M
- Li Liming
- Li Shengchao Alfred
- Li-Gao Ruifang
- Lieb Wolfgang
- Lin Kuang
- Liu Jianjun
- Loh Marie
- London Stephanie J
- Loomis Stephanie
- Loos Ruth J. F.
- Lu Yingchang
- Luan Jian’an
- Lumley Thomas
- Magnusson Patrik K. E.
- Mahajan Anubha
- Manichaikul Ani W
- Manunta Paolo
- Martin Nicholas G
- Mason Dan
- Matoba Nana
- Matsuda Koichi
- Mattsson Hannele
- Matullo Giuseppe
- McCarthy Mark I
- Medina-Gomez Carolina
- Medland Sarah E
- Mei Xue W
- Meidtner Karina
- Meisinger Christa
- Meitinger Thomas
- Meng Weihua
- Merriman Tony R
- Metspalu Andres
- Meyer Brian F
- Mezzavilla Massimo
- Milani Lili
- Millwood Iona Y
- Mohlke Karen L
- Momozawa Yukihide
- Montasser May E
- Montgomery Grant W
- Mook-Kanamori Dennis
- Moore Amy
- Moore Kristjan H S
- Morange Pierre-Emmanuel
- Moreno-Macías Hortensia
- Mori Trevor A
- Morrison Alanna C
- Muka Taulant
- Munroe Patricia B
- Munz Matthias
- Murakami Yoshinori
- Murray Alison D
- Mychaleckyj Josyf C
- Másson Gísli
- Mägi Reedik
- März Winfried
- Nalls Mike A
- Nauck Matthias
- Neville Matt J
- Nolte Ilja M
- North Kari E
- Nutile Teresa
- Nyholt Dale R
- Ober Carole
- Okada Yukinori
- Oldehinkel Albertine J
- Ong Ken K
- Orozco Lorena
- O’connell Jeffery R
- Padmanabhan Sandosh
- Palmas Walter
- Palmer Colin
- Palviainen Teemu
- Pankow James S
- Pasterkamp Gerard G
- Patin Etienne
- Pattaro Cristian
- Pattie Alison
- Pennell Craig E
- Perola Markus
- Perry John R. B.
- Perusse Louis
- Peyser Patricia A
- Pirastu Mario
- Pirastu Nicola
- Polasek Ozren
- Polderman Tinca J. C.
- Porteous David J
- Posthuma Danielle
- Poulter Neil
- Pramstaller Peter P
- Prasad Gauri
- Prasad Rashmi B
- Priyanka Tallapragada Divya Sri
- Psaty Bruce M
- Pálsson Gunnar
- Quintana-Murci Lluis
- Ralhan Sarju
- Rao Dabeeru C
- Rich Stephen S
- Ridker Paul M
- Rietveld Cornelius A
- Rioux John D
- Rivadeneira Fernando
- Rizzi Federica
- Robino Antonietta
- Rohde Rebecca
- Rotimi Charles
- Rotter Jerome I
- Rudan Igor
- Ruggiero Daniela
- Räikkönen Katri
- Saba Yasaman
- Sabanayagam Charumathi
- Sabater-Lleal Maria
- Sala Cinzia Felicita
- Salomaa Veikko
- Salvi Erika
- Sandow Kevin
- Sanghera Dharambir K
- Sapkota Bishwa R
- Sattar Naveed
- Schmidt Helena
- Schmidt Reinhold
- Schulze Matthias B
- Schunkert Heribert
- Schurmann Claudia
- Scott Laura J
- Scott Robert A
- Scott William R
- Sedaghati-Khayat Bahareh
- Sennblad Bengt
- Sever Peter J
- Sheu Wayne H-H
- Shi Yuan
- Shrestha Smeeta
- Shriner Daniel
- Shukla Sharvari Rahul
- Shuldiner Alan R
- Sigurdsson Jon K
- Sikka Timo Tonis
- Sim Xueling
- Singh Jai Rup
- Skotte Line
- Small Neil
- Smart Melissa C
- Smith Albert Vernon
- Smith Blair H
- Smith George Davey
- Smith Jennifer A
- Sotoodehnia Nona
- Spracklen Cassandra N
- Stanton Alice
- Stančáková Alena
- Starr John M
- Stefansdottir Lilja
- Stefansson Kari
- Straker Leon
- Strawbridge Rona J
- Sulem Patrick
- Sveinbjornsson Gardar
- Swertz Morris A
- Tai E-Shyong
- Tajuddin Salman M
- Taylor Adele M
- Taylor Kent D
- Terzikhan Natalie
- Teumer Alexander
- Tham Yih-Chung
- Thorleifsson Gudmar
- Thorsteinsdottir Unnur
- Tillander Annika
- Timpson Nicholas J
- Toniolo Daniela
- Tracy Russell P
- Tregouet David-Alexandre
- Trompet Stella
- Tuomi Tiinamaija
- Turman Constance
- Tusié-Luna Teresa
- Tzoulaki Ioanna
- Uitterlinden André G
- Vaccargiu Simona
- van Dam Rob M
- van den Berg Leonard H
- van der Harst Pim
- van der Laan Sander W
- van der Most Peter J
- van der Spek Ashley
- van Duijn Cornelia M
- van Eijk Kristel R
- van Heel David A
- van Rheenen Wouter
- van Rooij Frank J A
- van Setten Jessica
- Vangipurapu Jagadish
- Veldink Jan H
- Verweij Niek
- Viberti Clara
- Vitart Veronique
- Vollenweider Peter
- Vuoksimaa Eero
- Völker Uwe
- Wakil Salma M
- Waldenberger Melanie
- Walters Robin G
- Wander Gurpreet S
- Wang Carol A
- Wang Lihua
- Wang Ya Xing
- Wareham Nicholas J
- Warren Helen R
- Weir David R
- Whitfield John B
- Wijmenga Cisca
- Wild Sarah
- Wilson James F
- Wong Tien-Yin
- Wootton Robyn E
- Wright John
- Yajnik Chittaranjan S
- Yanek Lisa R
- Yang Jingyun
- Yao Jie
- Yousri Noha A
- Yu Lei
- Yuan Jian-Min
- Zemel Babette S
- Zeng Lingyao
- Zhang Liang
- Zhang Weihua
- Zhao Jing Hua
- Zhao Wei
- Zhou Jie
- Zonderman Alan B
- Publication venue
- Nature Communications
- Publication date
- 31/10/2020
- Field of study
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- Author
- Aaltonen L. (Lauri)
- Aaltonen V. (Vesa)
- Arvas M. (Mikko)
- Auge F. (Franck)
- Auranen A. (Annika)
- Auro K. (Kirsi)
- Auvinen P. (Paivi)
- Awaisa G. (Ghazal)
- Betts J. (Jo)
- Bhangale T. (Tushar)
- Bing N. (Nan)
- Biswas S. (Shameek)
- Blomster T. (Timo)
- Bowers N. (Natalie)
- Brein G. (Georg)
- Bronson P. (Paola)
- Call K. (Kathy)
- Carpen O. (Olli)
- Challis B. (Ben)
- Chang D. (Diana)
- Chatelain C. (Clement)
- Chen C.-Y. (Chia-Yen)
- Chen H. (Hao)
- Chen H. (Hubert)
- Chen X. (Xing)
- Chhibber A. (Aparna)
- Chu A. (Audrey)
- Close D. (David)
- Crohns M. (Marika)
- Dada A. (Alexander)
- Daly M. J. (Mark J.)
- Davis J. W. (Justin Wade)
- Diogo D. (Dorothee)
- Donner K. (Kati)
- Eaton S. (Susan)
- Ehm M. (Meg)
- Eicher J. (John)
- Eklund K. (Kari)
- Elenius K. (Klaus)
- Esmaeeli S. (Sahar)
- Farkkila M. (Martti)
- Fox C. (Caroline)
- Freimer N. B. (Nelson B.)
- Ganna A. (Andrea)
- Georgantas B. (Bob)
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- Ghosh S. (Soumitra)
- Gordillo J. E. (Jorge Esparza)
- Gormley P. (Padhraig)
- Gossel M. (Matthias)
- Greenberg S. (Steven)
- Hannula-Jouppi K. (Katariina)
- Harju J. (Jarmo)
- Harju T. (Terttu)
- Harvima I. (Ilkka)
- Hassan S. (Shabbeer)
- Hautala N. (Nina)
- Havulinna A. S. (Aki S.)
- Heap G. (Graham)
- Hedman A. (Asa)
- Heikkinen S. (Sami)
- Hendolin M. (Minna)
- Hiekkalinna T. (Tero)
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- Hoffman J. (Joshua)
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- Koulu L. (Leena)
- Kristiansson K. (Kati)
- Kujala U. (Urho)
- Kulkarni D. (Diptee)
- Kuopio T. (Teijo)
- Kurki M. (Mitja)
- Laakkonen E. (Eija)
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- Sipila T. P. (Timo P.)
- Sistonen T. (Tuuli)
- Smaoui N. (Nizar)
- Soderlund S. (Sanni)
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- Stitziel N. O. (Nathan O.)
- Strauss E. (Erich)
- Surma M. A. (Michal A.)
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- Tabuenca J. G. (Javier Gracia)
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- Taskinen M.-R. (Marja-Riitta)
- Teng E. (Edmond)
- Tienari P. (Pentti)
- Tuomi T. (Tiinamaija)
- Tuovila O. (Outi)
- Turunen J. (Joni)
- Usiskin K. (Keith)
- Uusitalo H. (Hannu)
- Uusitalo-Jarvinen H. (Hannele)
- Vainio S. (Seppo)
- Virolainen P. (Petri)
- Voutilainen M. (Markku)
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- Wang C. (Clarence)
- Wang X. (Xulong)
- Waring J. (Jeff)
- Waring J. (Jeffrey)
- Waterworth D. (Dawn)
- Whelan C. (Christopher)
- Wong R. (Regis)
- Wu Y. (Ying)
- Xu E. (Ethan)
- Xu F. (Fanli)
- Yang R. (Robert)
- Zhou W. (Wei)
- Ziemann A. (Adam)
- Publication venue
- Springer Nature
- Publication date
- 01/01/2019
- Field of study
Abstract
Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
- Author
- Aaltonen L. (Lauri)
- Aaltonen V. (Vesa)
- Abe N. (Namiko)
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- Kristiansson K. (Kati)
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- Lewis J. (Joshua)
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- Publication venue
- Springer Nature
- Publication date
- 01/01/2021
- Field of study
Abstract
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids
New insights into the genetic etiology of Alzheimer’s disease and related dementias
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- A David Smith
- Aaltonen L.
- Aaltonen V.
- Aarno Palotie
- Aarsland D.
- Aavikko M.
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- Abdelnour C.
- Abner E.
- Abraham R.
- Ad Adarmes-Gómez
- Adam Boxer
- Adam Ziemann
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- Adriana Gamboa
- Adrienne L Cupples
- Adrienne Tin
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- Aimee Pierce
- Aino Salminen
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- Alberto Benussi
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- Yeunjoo E Song
- Yi Zhao
- Ying Wu
- Yoav Ben-Shlomo
- Yogen Patel
- Younkin S. G.
- Yu C. -E.
- Yu L.
- Yuanchao Zhang
- Yuk Yee Leung
- Yunfeng Huang
- Yunju Yang
- Zare H.
- Zdenka Pausova
- Zhang X.
- Zhang Y.
- Zhao Y.
- Zhao Y.
- Zhou W.
- Zhu C.
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- Ziemann A.
- Zoia C. P.
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- Zulaica M.
- Zulma Sevillano
- Álvarez V.
- Åsa Hedman
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
New insights into the genetic etiology of Alzheimer’s disease and related dementias
- Author
- Aaltonen Lauri
- Aaltonen Vesa
- Aarsland Dag
- Aavikko Mervi
- Abalos Mariana Sanchez
- Abdelnour Carla
- Abner Erin
- Abraham Richard
- Adams Hieab
- Adams Perrie M.
- Adarmes-Gómez Ad
- Adarmes-Gómez Astrid D.
- Aguilera Nuria
- Aguilera Nuria
- Aguirre Alyssa
- Ahmad Shahzad
- Akinyemi Rufus O.
- Al-Chalabi Ammar
- Alarcón-Martín Emilio
- Albert Marilyn S.
- Albin Roger L.
- Alcolea Daniel
- Alegret Montserrat
- Ali Muhammad
- Allen Mariet
- Allende Irene Rosas
- Alonso María Dolores
- Alonso María Dolores
- Alvarez Ignacio
- Alvarez Lisa
- Amer-Ferrer Guillermo
- Amin Najaf
- Amouyel Philippe
- Anastasiou Anna
- Anastasiou Costas
- Andrade Victor
- Andreassen Ole A.
- Andreoni Simona
- Antequera Martirio
- Antikainen Riitta
- Antonell Anna
- Anttonen Vuokko
- Antúnez Carmen
- Aparicio Hugo J.
- Apostolova Liana G.
- Appollonio Ildebrando
- Arcaro Marina
- Archetti Silvana
- Armstrong Nicola
- Armstrong Nicola J.
- Arnold Steven E.
- Arosio Beatrice
- Arvas Mikko
- Assogna Francesca
- Asthana Sanjay
- Athanasiu Lavinia
- Atwood Craig S.
- Auge Franck
- Auranen Annika
- Auvinen Päivi
- Awaisa Ghazal
- Ayres Gayle
- Bacha Juan Ignacio
- Bahadori Maryam
- Bahrami Shahram
- Bailly Henri
- Baldwin Clinton T.
- Banaj Nerisa
- Baquero Miquel
- Barber Robert C.
- Barnes Lisa L.
- Barral Sandra
- Barral Sandra
- Bass Nicholas J.
- Bass Nick
- Bastiani Patrizia
- Bayer Anthony
- Beach Thomas G.
- Becker James T.
- Becker James T.
- Becker Tim
- Beecham Gary W.
- Beekly Duane
- Behrens Tim
- Beiser Alexa
- Belezhanska Diyana
- Bellenguez Céline
- Below Jennifer E.
- Below Jennifer E.
- Ben-Shlomo Yoav
- Benchek Penelope
- Benchek Penelope
- Benitez Bruno A.
- Bennett David
- Benussi Alberto
- Benussi Luisa
- Bergh Sverre
- Bernardo-Harrington Mateus
- Berr Claudine
- Bertelson John
- Besse Céline
- Bessi Valentina
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- Bhangale Tushar
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- Binetti Giuliano
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- Bird Thomas D.
- Bis Joshua C.
- Biswas Shameek
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- Bjerke Maria
- Blacker Deborah
- Blesa Rafael
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- Boeve Bradley F.
- Boland Anne
- Borroni Barbara
- Boschi Silvia
- Bosnes Ingunn
- Bossù Paola
- Bowen James D.
- Bowers Natalie
- Boxer Adam
- Brauer Matt
- Brayne Carol
- Brein Georg
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- Bressler Jan
- Breteler Monique
- Brewer James
- Brice Alexis
- Brodaty Henry
- Broeckhoven Christine Van
- Bronson Paola
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- Chasse Scott
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- Chauhan Ganesh
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- Chesi Alessandra
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- Comic Hata
- Conti Elisa
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- Costa Marcos R.
- Costantini Emanuele
- Cox Simon
- Craft Suzanne
- Craig David
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- Cuesta Carolina
- Cullum Munro
- Cummings Beryl
- Cupples Adrienne L.
- Custodero Carlo
- Daian Delphine
- Dalmasso Maria Carolina
- Daly Mark
- Damotte Vincent
- Daniele Antonio
- Darby Eveleen
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- Dartigues Jean-François
- Davies Chloe
- Davies Gail
- Davis Barbara
- Davis Justin Wade
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- de Mendonça Alexandre
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- Debette Stéphanie
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- del Ser Teodoro
- Deleuze Jean-François
- della Briotta Parola Pietro
- della Briotta Parolo Pietro
- Deloukas Panagiotis
- Deloukas Pangiotis
- Denning Nicola
- Deramecourt Vincent
- Deramerourt Vincent
- DeStefano Anita
- DeToledo John
- Dichgans Martin
- Dick Malcolm
- Dickson Dennis W.
- Diego Susana
- Diehl-Schmid Janine
- Diez-Fairen Mónica
- Diogo Dorothee
- Djurovic Srdjan
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- Donner Kati
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- Duara Ranjan
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- Dupuis Josée
- Duron Emmanuelle
- Düzel Emrah
- Eaton Susan
- Ehm Meg
- Eicher John
- Eiriksdottir Gudny
- Eklund Kari
- Elenius Klaus
- Elliott Amanda
- Engelborghs Sebastiaan
- Epelbaum Jacques
- Ertekin-Taner Nilüfer
- Escott-Price Valentina
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- Ferris Steven
- Feulner Thomas
- Fievet Nathalie
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- Franco-Macías Emlio
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- Froelich Lutz
- Frosch Matthew P.
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- Fulton-Howard Brian
- Fulton-Howard Brian
- Färkkilä Martti
- Gailhajenet Anna
- Galasko Douglas R.
- Galeano Pablo
- Galimberti Daniela
- Gamboa Adriana
- Ganguli Mary
- Ganna Andrea
- Garcia-Gonzalez Pablo
- Garcia-Madrona Sebastian
- Garcia-Ribas Guillermo
- Garcia-Tabuenca Javier
- García-Alberca Jose Maria
- García-González Pablo
- Garrote-Espina L.
- Garrote-Espina Lorena
- Gearing Marla
- Geerlings Mirjam
- Georgantas Bob
- George-Hyslop Peter St
- Germani Sandra
- Gerrish Amy
- Geschwind Daniel H.
- Ghanbari Mohsen
- Ghetti Bernardino
- Ghidoni Roberta
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- Gordillo Jorge Esparza
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- Guerreiro Rita
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- Gurling Hugh
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- Gwilliam Rhian
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- Gómez-Garre Pilar
- Haapasalo Annakaisa
- Habes Mohamad
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- Harold Denise
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- Hartmann Annette M.
- Harvima Ilkka
- Harwood Janet
- Hausner Lucrezia
- Haut Jacob
- Hautala Nina
- Havulinna Aki
- Head Elizabeth
- Heap Graham
- Heckbert Susan R.
- Hedman Åsa
- Heikkinen Sami
- Heilmann-Heimbach Stefanie
- Helisalmi Seppo
- Henderson Victor W.
- Hendolin Minna
- Heneka Michael T.
- Hernandez Michelle
- Hernández Isabel
- Herold Christine
- Heron Samuel
- Herrmann Martin J.
- Heun Reinhard
- Heuser Isabella
- Hevilla Saray
- Heyne Henrike
- Hiekkalinna Tero
- Hiltunen Mikko
- Hinttala Reetta
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- Hodges Angela
- Hofer Edith
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- Huentelman Matthew J.
- Hughes Timothy
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- Huilaja Laura
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- Hulsman Marc
- Humphrey Jack
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- Hynan Linda S.
- Hyvärinen Kati
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- Ibanez Laura
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- Parisi Joseph E.
- Parkkinen Jaakko
- Parnetti Lucilla
- Partanen Jukka
- Parveen Kayenat
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- Pastor Ana Belén
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- Paus Tomas
- Pausova Zdenka
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- Pijnenburg Yolande A. L.
- Pikkarainen Sampsa
- Pinchler Sabrina
- Pineda Juan A.
- Pineda-Sánchez R.
- Pineda-Sánchez Rocío
- Piras Fabrizio
- Piras Federica
- Pirilä Laura
- Pisanu Claudia
- Pitkäranta Anne
- Piñol-Ripoll Gerard
- Plenge Robert
- Podgornaia Anna
- Polak Thomas
- Politis Daniel G.
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- Popovic Relja
- Popp Julius
- Posthuma Danielle
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- Prestia Federico Ariel
- Priller Josef
- Proitsi Petra
- Prokic Ivana
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- Puerta Raquel
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- Quarless Danjuma
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- Raikkonen-Talvitie Katri
- Rainero Innocenzo
- Raj Ashok
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- van der Lugt Aad
- van Duijn Cornelia M.
- van Eldik Linda J.
- van Lent Debora Melo
- van Rooij Jeroen
- van Swieten John
- Vance Jeffery
- Vandenberghe Rik
- Vardarajan Badri N.
- Vardy Emma
- Vargas Liliana
- Vassar Robert
- Verhey Frans
- Vicente Maria Pilar
- Vidal Jean-Sébastien
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- Vigo-Ortega Rosario
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- Vinters Harry V.
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- Vivancos Liliana
- Vogelgsang Jonathan
- Vojinovic Dina
- Vonsattel Jean-Paul
- Voutilainen Markku
- Vyhnalek Martin
- Wadhawan Samir
- Wagner Michael
- Wallon David
- Wang Clarence
- Wang Li-San
- Wang Ruiqi
- Wang Yanbing
- Warden Donald
- Waring Jeff
- Waring Jeffrey
- Warner Nick
- Warren Jason D.
- Waterworth Dawn
- Weber Heike
- Weinhold Leonie
- Weinstein Galit
- Weintraub Sandra
- Welsh-Bohmer Kathleen A.
- Whelan Christopher
- Whitehead Patrice L.
- Wichmann H-Erich
- Wigmore Eleonor
- Wijsman Ellen M.
- Wilcock Gordon
- Wilhelmsen Kirk C.
- Williams Amy
- Williams Benjamin
- Williams Dylan
- Williams Julie
- Williamson Jennifer
- Wilms Henrik
- Wiltfang Jens
- Windle Gill
- Wingo Thomas S.
- Wisniewski Thomas
- Wittfeld Katharina
- Woltjer Randall L.
- Wong Regis
- Woods Bob
- Woon Martin
- Wright Clinton B.
- Wu Chuang-Kuo
- Wu Ying
- Xia Tai-he
- Xu Ethan
- Xu Fanli
- Yanek Lisa
- Yang Qiong
- Yang Yunju
- Yannakoulia Mary
- Yaqub Amber
- Younkin Steven G.
- Yu Chang-En
- Yu Lei
- Zare Habil
- Zhang Xiaoling
- Zhang Yuanchao
- Zhao Yi
- Zhao Yi
- Zhou Wei
- Zhu Congcong
- Zhu Xiongwei
- Ziemann Adam
- Zoia Chiara Paola
- Zompo Maria Del
- Zulaica Miren
- Álvarez Victoria
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/04/2022
- Field of study
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele