Genome-wide gene by lead exposure interaction analysis identifies UNC5D as a candidate gene for neurodevelopment

Wang, Zhaoxi; Claus Henn, Birgit; Wang, Chaolong; Wei, Yongyue; Su, Li; Sun, Ryan; Chen, Han; Wagner, Peter J.; Lu, Quan; Lin, Xihong; Wright, Robert; Bellinger, David; Kile, Molly; Mazumdar, Maitreyi; Tellez-Rojo, Martha Maria; Schnaas, Lourdes; Christiani, David C.

doi:10.1186/s12940-017-0288-3

Environmental Health

Table 3 Top SNPs demonstrating gene-environment interactions for both mental and motor composite scores

From: Genome-wide gene by lead exposure interaction analysis identifies UNC5D as a candidate gene for neurodevelopment

				MAF		Mental composite scores				Motor composite scores
SNP	Chr	Alleles (Minor/Ref)	Position (bp)	Mexico	Bangladesh	p _Max	p _Bang	p _meta	Dir^a	p _Max	p _Bang	p _meta	Dir^a	Gene
rs12071731	1	T/G	6,276,167	0.047	0.126	0.0035	0.011	0.00013	++	0.020	0.012	0.00065	++	RNF207
rs2552531	2	A/G	218,698,323	0.019	0.066	0.0063	0.018	0.00037	++	0.0050	0.0038	6.19E-05	++	TNS1
rs645163	2	A/G	219,682,257	0.186	0.184	0.013	0.022	0.00083	--	0.0086	0.020	0.00054	--	PRKAG3/CYP27A1/ WNT6/TTLL4/WNT10A
rs755773	4	A/G	32,628,884	0.193	0.230	0.079	0.0034	0.00086	--	0.184	0.00079	0.00075	--
rs11133230	4	A/G	32,640,520	0.280	0.336	0.101	0.00012	8.17E-05	--	0.139	9.87E-06	2.06E-05	--
rs920908	5	T/C	41,288,697	0.128	0.350	0.197	0.00041	0.00052	--	0.0032	0.022	0.00026	--	MROH2B/LOC102723740/ C6/PLCXD3
rs32897	5	A/G	76,250,972	0.132	0.138	0.021	0.017	0.00099	--	0.014	0.020	0.00077	--	CRHBP
rs12201457	6	T/C	117,330,177	0.189	0.070	0.065	1.53E-05	9.71E-06	--	0.387	9.72E-05	0.00053	--	RFX6
rs3112346	7	A/G	135,387,495	0.270	0.268	0.032	0.0044	0.00042	--	0.069	0.0045	0.00092	--	SLC13A4
rs28694796	7	A/G	155,403,168	0.081	0.068	0.025	0.0028	0.00022	--	0.00063	0.0093	2.72E-05	--	EN2/RBM33/CNPY1/ SHH
rs10503970	8	A/G	34,866,368	0.077	0.116	0.0018	0.0073	4.98E-05	++	0.0019	0.031	0.00026	++	UNC5D
rs4269538	8	T/C	34,889,071	0.094	0.130	0.0019	0.055	0.00050	--	0.023	0.011	0.00068	--	UNC5D
rs7837686	8	T/C	142,674,928	0.441	0.449	0.040	0.0051	0.00058	++	0.013	0.018	0.00069	++	MROH5/MIR1302–7
rs6475430	9	T/C	20,430,468	0.250	0.338	0.050	0.00043	9.38E-05	--	0.0058	0.019	0.00035	--	MLLT3
rs10898112	11	A/G	69,934,085	0.243	0.102	0.038	0.0061	0.00066	--	0.233	0.00073	0.00099	--	ANO1
rs2168819	11	A/G	80,964,065	0.340	0.439	0.079	0.0014	0.00042	++	0.014	0.018	0.00070	++
rs1950593	14	A/G	27,408,826	0.118	0.186	0.085	0.00087	0.00031	++	0.014	0.0077	0.00032	++	MIR4307
rs11848381	14	A/G	55,188,149	0.124	0.219	0.0071	0.041	0.00097	++	0.0010	0.031	0.00016	++	SAMD4A

SNP Single-nucleotide polymorphism MAF minor allele frequency
All models adjusted for child’s gender, child’s age at time of neurodevelopment testing, gestational age, parity, maternal education (binary), environmental tobacco smoke exposure (binary), and first two principal components of population stratification
^aEffects of gene-environment interaction on the neurodevelopmental outcomes. “+”: increased risk; “-”: protective effect. The first “+/−” represents the effect observed in Mexico cohort, and the second “+/−” represents the effect observed in Bangladesh cohort

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ISSN: 1476-069X

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