Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

PLoS Genet
Authors
Keywords
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

Year of Publication
2014
Journal
PLoS Genet
Volume
10
Issue
7
Pages
e1004508
Date Published
2014 Jul
ISSN
1553-7404
URL
DOI
10.1371/journal.pgen.1004508
PubMed ID
25078964
PubMed Central ID
PMC4117451
Links
Grant list
UL1RR025005 / RR / NCRR NIH HHS / United States
G0100266 / Medical Research Council / United Kingdom
084723/Z/08/Z / Wellcome Trust / United Kingdom
RP-PG-0310-1002 / Department of Health / United Kingdom
R01HL59367 / HL / NHLBI NIH HHS / United States
AA13320 / AA / NIAAA NIH HHS / United States
HHSN268201100005C / PHS HHS / United States
R01DK8925601 / DK / NIDDK NIH HHS / United States
DA12854 / DA / NIDA NIH HHS / United States
AA13321 / AA / NIAAA NIH HHS / United States
AA10248 / AA / NIAAA NIH HHS / United States
HHSN268201100009C / PHS HHS / United States
G0700931 / Medical Research Council / United Kingdom
5R01MH63706:02 / MH / NIMH NIH HHS / United States
0927310 / Wellcome Trust / United Kingdom
P30 DK079637 / DK / NIDDK NIH HHS / United States
T32 HL091823 / HL / NHLBI NIH HHS / United States
1RL1MH083268-01 / MH / NIMH NIH HHS / United States
HHSN268200625226C / PHS HHS / United States
MC_UP_0801/1 / Medical Research Council / United Kingdom
MR/K026992/1 / Medical Research Council / United Kingdom
G0500539 / Medical Research Council / United Kingdom
HHSN268201100010C / PHS HHS / United States
102215 / Wellcome Trust / United Kingdom
MC_UU_12015/1 / Medical Research Council / United Kingdom
U01HG004402 / HG / NHGRI NIH HHS / United States
0927310 / Medical Research Council / United Kingdom
097117 / Wellcome Trust / United Kingdom
WT083431MA / Wellcome Trust / United Kingdom
MC_PC_15018 / Medical Research Council / United Kingdom
HHSN268201100008C / PHS HHS / United States
HHSN268201100012C / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
MC_UU_12013/1 / Medical Research Council / United Kingdom
G0701863 / Medical Research Council / United Kingdom
MC_UU_12013/4 / Medical Research Council / United Kingdom
CZD/16/6/4 / Chief Scientist Office / United Kingdom
MC_PC_U127561128 / Medical Research Council / United Kingdom
RG/09/012/28096 / British Heart Foundation / United Kingdom
G0601966 / Medical Research Council / United Kingdom
HHSN268201100007C / PHS HHS / United States
AA014041 / AA / NIAAA NIH HHS / United States
MR/K006584/1 / Medical Research Council / United Kingdom
MR/K013351/1 / Medical Research Council / United Kingdom
HHSN268201100011C / PHS HHS / United States
MC_U106179471 / Medical Research Council / United Kingdom
5R01HL087679-02 / HL / NHLBI NIH HHS / United States
BB/F019394/1 / Biotechnology and Biological Sciences Research Council / United Kingdom
HHSN268201100006C / PHS HHS / United States
G1002319 / Medical Research Council / United Kingdom
AA07535 / AA / NIAAA NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
AA13326 / AA / NIAAA NIH HHS / United States
G9815508 / Medical Research Council / United Kingdom
G0600705 / Medical Research Council / United Kingdom
R01HL086694 / HL / NHLBI NIH HHS / United States