| Title: | Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood |
| Journal: | American Journal of Human Genetics |
| Published: | 10 May 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/29754766/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2018.03.021 |
| URL: | http://www.cell.com/article/S0002929718301101/pdf |
Publication 8525
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Abstract
Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on ∼150,000 individuals give a higher accuracy than LDSC estimates based on ∼400,000 individuals (from combined meta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.</p>
305 Authors
- Guiyan Ni
- Gerhard Moser
- Schizophrenia Working Group of the Psychiatric Genomics Consortium
- Stephan Ripke
- Benjamin M. Neale
- Aiden Corvin
- James T.R. Walters
- Kai-How Farh
- Peter A. Holmans
- Phil Lee
- Brendan Bulik-Sullivan
- David A. Collier
- Hailiang Huang
- Tune H. Pers
- Ingrid Agartz
- Esben Agerbo
- Margot Albus
- Madeline Alexander
- Farooq Amin
- Silviu A. Bacanu
- Martin Begemann
- Richard A. Belliveau
- Judit Bene
- Sarah E. Bergen
- Elizabeth Bevilacqua
- Tim B. Bigdeli
- Donald W. Black
- Richard Bruggeman
- Nancy G. Buccola
- Randy L. Buckner
- William Byerley
- Wiepke Cahn
- Guiqing Cai
- Dominique Campion
- Rita M. Cantor
- Vaughan J. Carr
- Noa Carrera
- Stanley V. Catts
- Kimberly D. Chambert
- Raymond C.K. Chan
- Ronald Y.L. Chen
- Eric Y.H. Chen
- Wei Cheng
- Eric F.C. Cheung
- Siow Ann Chong
- C. Robert Cloninger
- David Cohen
- Nadine Cohen
- Paul Cormican
- Nick Craddock
- James J. Crowley
- David Curtis
- Michael Davidson
- Kenneth L. Davis
- Franziska Degenhardt
- Jurgen Del Favero
- Ditte Demontis
- Dimitris Dikeos
- Timothy Dinan
- Srdjan Djurovic
- Gary Donohoe
- Elodie Drapeau
- Jubao Duan
- Frank Dudbridge
- Naser Durmishi
- Peter Eichhammer
- Johan Eriksson
- Valentina Escott-Price
- Laurent Essioux
- Ayman H. Fanous
- Martilias S. Farrell
- Josef Frank
- Lude Franke
- Robert Freedman
- Nelson B. Freimer
- Marion Friedl
- Joseph I. Friedman
- Menachem Fromer
- Giulio Genovese
- Lyudmila Georgieva
- Ina Giegling
- Paola Giusti-Rodríguez
- Stephanie Godard
- Jacqueline I. Goldstein
- Vera Golimbet
- Srihari Gopal
- Jacob Gratten
- Lieuwe de Haan
- Christian Hammer
- Marian L. Hamshere
- Mark Hansen
- Thomas Hansen
- Vahram Haroutunian
- Annette M. Hartmann
- Frans A. Henskens
- Stefan Herms
- Joel N. Hirschhorn
- Per Hoffmann
- Andrea Hofman
- Mads V. Hollegaard
- David M. Hougaard
- Masashi Ikeda
- Inge Joa
- Antonio Juliá
- René S. Kahn
- Luba Kalaydjieva
- Sena Karachanak-Yankova
- Juha Karjalainen
- David Kavanagh
- Matthew C. Keller
- James L. Kennedy
- Andrey Khrunin
- Yunjung Kim
- Janis Klovins
- James A. Knowles
- Bettina Konte
- Vaidutis Kucinskas
- Zita Ausrele Kucinskiene
- Hana Kuzelova-Ptackova
- Anna K. Kähler
- Claudine Laurent
- Jimmy Lee Chee Keong
- Sophie E. Legge
- Bernard Lerer
- Miaoxin Li
- Tao Li
- Kung-Yee Liang
- Jeffrey Lieberman
- Svetlana Limborska
- Carmel M. Loughland
- Jan Lubinski
- Jouko Lönnqvist
- Milan Macek
- Patrik K.E. Magnusson
- Brion S. Maher
- Wolfgang Maier
- Jacques Mallet
- Sara Marsal
- Manuel Mattheisen
- Morten Mattingsda
- Robert W. McCarley
- Colm McDonald
- Andrew M. McIntosh
- Sandra Meier
- Carin J. Meijer
- Bela Melegh
- Ingrid Melle
- Raquelle I. Mesholam-Gately
- Andres Metspalu
- Patricia T. Michie
- Lili Milani
- Vihra Milanova
- Younes Mokrab
- Derek W. Morris
- Ole Mors
- Kieran C. Murphy
- Robin M. Murray
- Inez Myin-Germeys
- Bertram Müller-Myhsok
- Mari Nelis
- Igor Nenadic
- Deborah A. Nertney
- Gerald Nestadt
- Kristin K. Nicodemus
- Liene Nikitina-Zake
- Laura Nisenbaum
- Annelie Nordin
- Eadbhard O'Callaghan
- Colm O'Dushlaine
- F. Anthony O'Neill
- Sang-Yun Oh
- Ann Olinc
- Line Olsen
- Jim Van Os
- Psychosis Endophenotypes International Consortium
- Christos Pantelis
- George N. Papadimitriou
- Sergi Papio
- Elena Parkhomenko
- Michele T. Pato
- Tiina Paunio
- Milica Pejovic-Milovancevic
- Diana O. Perkins
- Olli Pietiläinenl
- Jonathan Pimm
- Andrew J. Pocklington
- John Powell
- Alkes Price
- Ann E. Pulver
- Shaun M. Purcell
- Digby Quested
- Henrik B. Rasmussen
- Abraham Reichenberg
- Mark A. Reimers
- Alexander L. Richards
- Joshua L. Roffman
- Panos Roussos
- Douglas M. Ruderfer
- Veikko Salomaa
- Alan R. Sanders
- Ulrich Schall
- Christian R. Schubert
- Thomas G. Schulze
- Sibylle G. Schwab
- Edward M. Scolnick
- Rodney J. Scott
- Larry J. Seidman
- Jianxin Shi
- Engilbert Sigurdsson
- Teimuraz Silagadze
- Jeremy M. Silverman
- Kang Sim
- Petr Slominsky
- Jordan W. Smoller
- Hon-Cheong So
- Chris C.A. Spencer
- Eli A. Stah
- Hreinn Stefansson
- Stacy Steinberg
- Elisabeth Stogmann
- Richard E. Straub
- Eric Strengman
- Jana Strohmaier
- T. Scott Stroup
- Mythily Subramaniam
- Jaana Suvisaari
- Dragan M. Svrakic
- Jin P. Szatkiewicz
- Erik Söderman
- Srinivas Thirumalai
- Draga Toncheva
- Sarah Tosato
- Juha Veijola
- John Waddington
- Dermot Walsh
- Dai Wang
- Qiang Wang
- Bradley T. Webb
- Mark Weiser
- Dieter B. Wildenauer
- Nigel M. Williams
- Stephanie Williams
- Stephanie H. Witt
- Aaron R. Wolen
- Emily H.M. Wong
- Brandon K. Wormley
- Hualin Simon Xi
- Clement C. Zai
- Xuebin Zheng
- Fritz Zimprich
- Kari Stefansson
- Peter M. Visscher
- Wellcome Trust Case-Control Consortium
- Rolf Adolfsson
- Ole A. Andreassen
- Douglas H.R. Blackwood
- Elvira Bramon
- Joseph D. Buxbaum
- Anders D. Børglum
- Sven Cichon
- Ariel Darvasi
- Enrico Domenici
- Hannelore Ehrenreich
- Tõnu Esko
- Pablo V. Gejman
- Michael Gill
- Hugh Gurling
- Christina M. Hultman
- Nakao Iwata
- Assen V. Jablensky
- Erik G. Jönsson
- Kenneth S. Kendler
- George Kirov
- Jo Knight
- Todd Lencz
- Douglas F. Levinson
- Qingqin S. Li
- Jianjun Liu
- Anil K. Malhotra
- Steven A. McCarrol
- Andrew McQuillin
- Jennifer L. Moran
- Preben B. Mortensen
- Bryan J. Mowry
- Markus M. Nöthen
- Roel A. Ophoff
- Michael J. Owen
- Aarno Palotie
- Carlos N. Pato
- Tracey L. Petryshen
- Danielle Posthuma
- Marcella Rietsche
- Brien P. Riley
- Dan Rujescu
- Pak C. Sham
- Pamela Sklar
- David St Clair
- Daniel R. Weinberger
- Jens R. Wendland
- Thomas Werge
- Mark J. Daly
- Patrick F. Sullivan
- Michael C. O'Donovan
- Naomi R. Wray
- S. Hong Lee
1 Application
| Application ID | Title |
|---|---|
| 14575 | Whole-genome approaches for dissecting (shared) genetic architecture and individual risk prediction of complex traits in human populations |
Enabling scientific discoveries that improve human health