Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index
Author(s)
Type
Journal Article
Abstract
The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a
novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The
method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups.
We applied the method to .56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead
SNPs were carried forward for replication in five family-based studies (of ,4,000 trios). Two SNPs replicated: the paternal
rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10
gene) increased BMI equally (beta = 0.11 (SD), P,0.0027) compared to the respective maternal alleles. Real-time PCR
experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on
parental origin of the SNPs alleles (P,0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated
individuals to identify POEs and demonstrates that they play an important role in adult obesity.
novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The
method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups.
We applied the method to .56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead
SNPs were carried forward for replication in five family-based studies (of ,4,000 trios). Two SNPs replicated: the paternal
rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10
gene) increased BMI equally (beta = 0.11 (SD), P,0.0027) compared to the respective maternal alleles. Real-time PCR
experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on
parental origin of the SNPs alleles (P,0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated
individuals to identify POEs and demonstrates that they play an important role in adult obesity.
Date Issued
2014-07-31
Date Acceptance
2014-05-14
Citation
PLOS Genetics, 2014, 10 (7)
ISSN
1553-7390
Publisher
Public Library of Science
Journal / Book Title
PLOS Genetics
Volume
10
Issue
7
Copyright Statement
© 2014 Hoggart et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
G0700931
G0601966
G1002319
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENETICS & HEREDITY
QUANTITATIVE TRAIT LOCI
LINKAGE ANALYSIS
OBESITY
CHILDREN
ASSOCIATIONS
PENETRANCE
ALCOHOLISM
VARIANCES
FAMILIES
GENES
Publication Status
Published
Article Number
e1004508