Directional dominance on stature and cognition in diverse human populations
Author(s)
Type
Journal Article
Abstract
Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is 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), 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 runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). 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 evidence 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 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.
Date Issued
2015-07-01
Date Acceptance
2015-05-28
Citation
Nature, 2015, 523 (7561), pp.459-462
ISSN
0028-0836
Publisher
Nature Publishing Group
Start Page
459
End Page
462
Journal / Book Title
Nature
Volume
523
Issue
7561
Copyright Statement
© 2015 Macmillan Publishers Limited. All rights reserved.
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000358378900036&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
RDC02 79560
n/a
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Biological Evolution
Blood Pressure
Body Height
Cholesterol, LDL
Cognition
Cohort Studies
Educational Status
Female
Forced Expiratory Volume
Genome, Human
Homozygote
Humans
Lung Volume Measurements
Male
Phenotype
BioBank Japan Project
General Science & Technology
MD Multidisciplinary
Publication Status
Published