Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
31303263
TITLE
Comparing Within- and Between-Family Polygenic Score Prediction.
ABSTRACT
Polygenic scores are a popular tool for prediction of complex traits. However, prediction estimates in samples of unrelated participants can include effects of population stratification, assortative mating, and environmentally mediated parental genetic effects, a form of genotype-environment correlation (rGE). Comparing genome-wide polygenic score (GPS) predictions in unrelated individuals with predictions between siblings in a within-family design is a powerful approach to identify these different sources of prediction. Here, we compared within- to between-family GPS predictions of eight outcomes (anthropometric, cognitive, personality, and health) for eight corresponding GPSs. The outcomes were assessed in up to 2,366 dizygotic (DZ) twin pairs from the Twins Early Development Study from age 12 to age 21. To account for family clustering, we used mixed-effects modeling, simultaneously estimating within- and between-family effects for target- and cross-trait GPS prediction of the outcomes. There were three main findings: (1) DZ twin GPS differences predicted DZ differences in height, BMI, intelligence, educational achievement, and ADHD symptoms; (2) target and cross-trait analyses indicated that GPS prediction estimates for cognitive traits (intelligence and educational achievement) were on average 60% greater between families than within families, but this was not the case for non-cognitive traits; and (3) much of this within- and between-family difference for cognitive traits disappeared after controlling for family socio-economic status (SES), suggesting that SES is a major source of between-family prediction through rGE mechanisms. These results provide insights into the patterns by which rGE contributes to GPS prediction, while ruling out confounding due to population stratification and assortative mating.
Copyright 2019 The Authors. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2019 08 01
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2019/04/11
accepted 2019/06/06
pubmed 2019/07/16 06:00
medline 2020/03/17 06:00
entrez 2019/07/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Selzam S Selzam Saskia S Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. Electronic address: saskia.selzam@kcl.ac.uk.
Ritchie SJ Ritchie Stuart J SJ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
Pingault JB Pingault Jean-Baptiste JB Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK; Division of Psychology and Language Sciences, University College London, London WC1H 0AP, UK.
Reynolds CA Reynolds Chandra A CA Department of Psychology, University of California Riverside, Riverside, CA 92521, USA.
O'Reilly PF O'Reilly Paul F PF Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK; Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA.
Plomin R Plomin Robert R Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
INVESTIGATORS
JOURNAL
VOLUME: 105
ISSUE: 2
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2019
MONTH: 08
DAY: 01
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1537-6605
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
MR/M021475/1 Medical Research Council United Kingdom
G0901245 Medical Research Council United Kingdom
MR/N015746/1 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
KEYWORD
complex trait prediction
gene-environment correlation
gene-environment interplay
genetic nurture
polygenic score prediction
socio-economic status
within-family analysis
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Child
Cognition physiology
Cognition Disorders physiopathology
Diseases in Twins genetics
Educational Status genetics
Family genetics
Female genetics
Genes genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Male genetics
Multifactorial Inheritance genetics
Neurodevelopmental Disorders pathology
Phenotype pathology
Polymorphism, Single Nucleotide pathology
Schizophrenia physiopathology
Young Adult physiopathology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's