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| PMID |
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| TITLE |
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| Comparing Within- and Between-Family Polygenic Score Prediction. |
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| ABSTRACT |
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| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| 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 |
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| 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. |
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| INVESTIGATORS |
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| 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 |
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| MEDLINE JOURNAL |
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| MEDLINETA: Am J Hum Genet |
| COUNTRY: United States |
| ISSNLINKING: 0002-9297 |
| NLMUNIQUEID: 0370475 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Comparative Study |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
| Twin Study |
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| COMMENTS AND CORRECTIONS |
|
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| 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 |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| complex trait prediction |
| gene-environment correlation |
| gene-environment interplay |
| genetic nurture |
| polygenic score prediction |
| socio-economic status |
| within-family analysis |
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| MESH HEADINGS |
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| 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 |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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