Study Report

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Basic Info

Reference	Pickard, B. S., 2006 PMID: 16819533
Citation	Pickard, B. S., M. P. Malloy, et al. (2006). "Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder." Mol Psychiatry 11(9): 847-857.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	368 bipolar disorder cases, 386 schizophrenia cases and 458 controls
SNP/Region/Marker Size	27 SNPs
Predominant Ethnicity	Caucasian
Population	Scottish

Detail Info

Sample Status	368 bipolar disorder cases and 386 schizophrenia cases comprised of patients of hospitals in southeast and south central Scotland
Technique	typed at Illumina Inc., San Diego, CA, USA using their proprietorial bead-array technology
Statistical Method	Formatted genotype data were analysed using Cocaphase in order to derive P-values for both single marker associations and also two-, three- and four-marker global and individual haplotype tests.
Result Summary	This identified two discrete regions of disease risk within the GRIK4 locus: three single single nucleotide polymorphism (SNP) markers with a corresponding underlying haplotype associated with susceptibility to schizophrenia (P=0.0005, odds ratio (OR) of 1.453, 95% CI 1.182-1.787) and two single SNP markers and a haplotype associated with a protective effect against bipolar disorder (P=0.0002, OR of 0.624, 95% CI 0.485-0.802). After permutation analysis to correct for multiple testing, schizophrenia and bipolar disorder haplotypes remained significant (P=0.0430, s.e. 0.0064 and P=0.0190, s.e. 0.0043, respectively). We propose that these convergent cytogenetic and genetic findings provide molecular evidence for common aetiologies for different psychiatric conditions and further support the 'glutamate hypothesis' of psychotic illness.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 27)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs2156635	GRIK4	C/G	P-value = 0.081 between BPD cases and controls; P-value = 0.041 between all cases and controls		Positive
rs2000869	GRIK4	A/G	P-value = 0.484 between BPD cases and controls; P-value = 0.677 between all cases and controls		Negative
rs2276319	GRIK4	A/G	P-value = 0.434 between BPD cases and controls; P-value = 0.675 between all cases and controls		Negative
rs2187495	GRIK4	C/T	P-value = 0.157 between BPD cases and controls; P-value = 0.357 between all cases and controls		Negative
rs2852217	GRIK4	C/T	P-value = 0.136 between BPD cases and controls; P-value = 0.175 between all cases and controls		Negative
rs2282586	GRIK4	A/G	P-value = 0.02 between BPD cases and controls; P-value = 0.058 between all cases and controls	it was associated with bipolar disorder it was associated with bipolar disorder	Positive
rs3133226	GRIK4	C/T	P-value = 0.965 between BPD cases and controls; P-value = 0.904 between all cases and controls		Negative
rs3132780	GRIK4	A/G	P-value = 0.708 between BPD cases and controls; P-value = 0.514 between all cases and controls		Negative
rs1954787	GRIK4	C/T	P-value = 0.701 between BPD cases and controls; P-value = 0.515 between all cases and controls		Negative
rs1944522	GRIK4	C/T	P-value = 0.216 between BPD cases and controls; P-value = 0.405 between all cases and controls		Negative
rs6589832	GRIK4	A/G	P-value = 0.365 between BPD cases and controls; P-value = 0.833 between all cases and controls		Negative
rs6589846	GRIK4	G/T	P-value = 0.704 between BPD cases and controls; P-value = 0.141 between all cases and controls		Negative
rs7111184	GRIK4	G/T	P-value = 0.725 between BPD cases and controls; P-value = 0.736 between all cases and controls		Negative
rs7925270	GRIK4	C/T	P-value = 0.387 between BPD cases and controls; P-value = 0.695 between all cases and controls		Negative
rs7928347	GRIK4	C/T	P-value = 0.693 between BPD cases and controls; P-value = 0.382 between all cases and controls		Negative
rs879602	GRIK4	C/T	P-value = 0.557 between BPD cases and controls; P-value = 0.936 between all cases and controls		Negative
rs948028	GRIK4	A/C	P-value = 0.991 between BPD cases and controls; P-value = 0.687 between all cases and controls		Negative
rs949054	GRIK4	C/T	P-value = 0.315 between BPD cases and controls; P-value = 0.509 between all cases and controls		Negative
rs949056	GRIK4	A/G	P-value = 0.162 between BPD cases and controls; P-value = 0.476 between all cases and controls		Negative
rs3133855	GRIK4	C/T	P-value = 0.549 between BPD cases and controls; P-value = 0.624 between all cases and controls		Negative
rs4245040	GRIK4	C/T	P-value = 0.269 between BPD cases and controls; P-value = 0.25 between all cases and controls		Negative
rs433110	GRIK4	A/G	P-value = 0.835 between BPD cases and controls; P-value = 0.362 between all cases and controls		Negative
rs4430518	GRIK4	G/T	P-value = 0.653 between BPD cases and controls; P-value = 0.244 between all cases and controls		Negative
rs4582985	GRIK4	C/G	P-value = 0.286 between BPD cases and controls; P-value = 0.621 between all cases and controls		Negative
rs4935752	GRIK4	A/C	P-value = 0.584 between BPD cases and controls; P-value = 0.022 between all cases and controls		Positive
rs513548	GRIK4	C/T	P-value = 0.375 between BPD cases and controls; P-value = 0.786 between all cases and controls		Negative
rs602104	GRIK4 HMGB1P42	C/T	P-value = 0.003 between BPD cases and controls; P-value = 0.028 between all cases and controls	it was associated with bipolar disorder it was associated with bipolar disorder	Positive

Haplotypes reported by this study for BD (count: 89)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs2156635 - rs949056 - rs949054 - rs602104		GRIK4	P-value = 0.311 between SCZ cases and controls; P-value = 0.117 between all cases and controls		Negative
rs2187495 - rs3132780		GRIK4	P-value = 0.312 between BPD cases and controls; P-value = 0.495 between all cases and controls		Negative
rs2156635 - rs949056		GRIK4	P-value = 0.269 between BPD cases and controls; P-value = 0.027 between all cases and controls		Positive
rs2156635 - rs949056 - rs949054		GRIK4	P-value = 0.446 between BPD cases and controls; P-value = 0.129 between all cases and controls		Negative
rs2276319 - rs513548		GRIK4	P-value = 0.402 between BPD cases and controls; P-value = 0.472 between all cases and controls		Negative
rs2276319 - rs513548 - rs2282586		GRIK4	P-value = 0.039 between BPD cases and controls; P-value = 0.186 between all cases and controls		Positive
rs2187495 - rs3132780 - rs948028		GRIK4	P-value = 0.459 between BPD cases and controls; P-value = 0.508 between all cases and controls		Negative
rs2187495 - rs3132780 - rs948028 - rs2852217		GRIK4	P-value = 0.723 between SCZ cases and controls; P-value = 0.774 between all cases and controls		Negative
rs1954787 - rs4935752		GRIK4	P-value = 0.665 between BPD cases and controls; P-value = 0.088 between all cases and controls		Negative
rs1954787 - rs4935752 - rs6589846		GRIK4	P-value = 0.927 between BPD cases and controls; P-value = 0.287 between all cases and controls		Negative
rs2000869 - rs7479743 - rs6589832		GRIK4	P-value = 0.498 between BPD cases and controls; P-value = 0.391 between all cases and controls		Positive
rs2000869 - rs7479743 - rs6589832 - rs7925270		GRIK4	P-value = 0.246 between SCZ cases and controls; P-value = 0.483 between all cases and controls		Negative
rs1954787 - rs4935752 - rs6589846 - rs4430518		GRIK4	P-value = 0.562 between SCZ cases and controls; P-value = 0.32 between all cases and controls		Negative
rs2000869 - rs7479743		GRIK4	P-value = 0.421 between BPD cases and controls; P-value = 0.448 between all cases and controls		Negative
rs4430518 - rs433110 - rs7111184		GRIK4	P-value = 0.993 between BPD cases and controls; P-value = 0.855 between all cases and controls		Negative
rs4430518 - rs433110 - rs7111184 - rs2156635		GRIK4	P-value = 0.904 between SCZ cases and controls; P-value = 0.758 between all cases and controls		Negative
rs4935752 - rs6589846		GRIK4	P-value = 0.706 between BPD cases and controls; P-value = 0.103 between all cases and controls		Negative
rs4935752 - rs6589846 - rs4430518		GRIK4	P-value = 0.354 between BPD cases and controls; P-value = 0.16 between all cases and controls		Negative
rs4935752 - rs6589846 - rs4430518 - rs433110		GRIK4	P-value = 0.434 between SCZ cases and controls; P-value = 0.128 between all cases and controls		Negative
rs513548 - rs2282586		GRIK4	P-value = 0.03 between BPD cases and controls; P-value = 0.093 between all cases and controls		Positive
rs513548 - rs2282586	T-G	GRIK4	P-value = 0.0037		Positive
rs513548 - rs2282586 - rs1944522		GRIK4	P-value = 0.01 between BPD cases and controls; P-value = 0.054 between all cases and controls		Positive
rs3133855 - rs3133226 - rs2187495 - rs3132780		GRIK4	P-value = 0.594 between SCZ cases and controls; P-value = 0.824 between all cases and controls		Negative
rs4245040 - rs7928347		GRIK4	P-value = 0.05 between BPD cases and controls; P-value = 0.089 between all cases and controls		Negative
rs4245040 - rs7928347 - rs2000869		GRIK4	P-value = 0.187 between BPD cases and controls; P-value = 0.288 between all cases and controls		Positive
rs4245040 - rs7928347 - rs2000869 - rs7479743		GRIK4	P-value = 0.158 between SCZ cases and controls; P-value = 0.221 between all cases and controls		Negative
rs433110 - rs7111184		GRIK4	P-value = 0.988 between BPD cases and controls; P-value = 0.606 between all cases and controls		Negative
rs433110 - rs7111184 - rs2156635		GRIK4	P-value = 0.688 between BPD cases and controls; P-value = 0.57 between all cases and controls		Negative
rs433110 - rs7111184 - rs2156635 - rs949056		GRIK4	P-value = 0.917 between SCZ cases and controls; P-value = 0.707 between all cases and controls		Negative
rs4430518 - rs433110		GRIK4	P-value = 0.918 between BPD cases and controls; P-value = 0.769 between all cases and controls		Negative
rs3132780 - rs948028 - rs2852217		GRIK4	P-value = 0.54 between BPD cases and controls; P-value = 0.543 between all cases and controls		Negative
rs3132780 - rs948028		GRIK4	P-value = 0.954 between BPD cases and controls; P-value = 0.779 between all cases and controls		Negative
rs3133226 - rs2187495		GRIK4	P-value = 0.179 between BPD cases and controls; P-value = 0.492 between all cases and controls		Negative
rs3132780 - rs948028 - rs2852217 - rs879602		GRIK4	P-value = 0.022 between SCZ cases and controls; P-value = 0.171 between all cases and controls		Positive
rs3133226 - rs2187495 - rs3132780 - rs948028		GRIK4	P-value = 0.503 between SCZ cases and controls; P-value = 0.597 between all cases and controls		Negative
rs3133226 - rs2187495 - rs3132780		GRIK4	P-value = 0.326 between BPD cases and controls; P-value = 0.564 between all cases and controls		Negative
rs3133855 - rs3133226 - rs2187495		GRIK4	P-value = 0.485 between BPD cases and controls; P-value = 0.885 between all cases and controls		Negative
rs3133855 - rs3133226		GRIK4	P-value = 0.957 between BPD cases and controls; P-value = 0.971 between all cases and controls		Negative
rs2276319 - rs513548 - rs2282586 - rs1944522		GRIK4	P-value = 0.015 between SCZ cases and controls; P-value = 0.113 between all cases and controls		Positive
rs2276319 - rs513548 - rs2282586	A-T-G	GRIK4	P-value = 0.004		Positive
rs2282586 - rs1944522		GRIK4	P-value = 0.002 between BPD cases and controls; P-value = 0.048 between all cases and controls	These positionally bi-partite findings were further supporte...... These positionally bi-partite findings were further supported by a sliding window global analysis of haplotypes of lengths two to four, such that distinct clusters of significant P-values were observed in bipolar disorder (best global haplotype, SNPs 26 and 27; P = 0.002). The global haplotype approached significance after permutation analysis (P = 0.049, s.e. 0.007). More...	Positive
rs2276319 - rs513548 - rs2282586 - rs1944522	A-T-G-C	GRIK4	P-value = 0.0035		Positive
rs2852217 - rs879602		GRIK4	P-value = 0.034 between BPD cases and controls; P-value = 0.232 between all cases and controls		Positive
rs2282586 - rs1944522	G-C	GRIK4	P-value = 0.0002, Correction P-value = 0.0190	a two-SNP haplotype (GC, SNPs 26 and 27) showed the greatest...... a two-SNP haplotype (GC, SNPs 26 and 27) showed the greatest significance (P = 0.0002, est. freq. cases: 0.16, est. freq. controls: 0.23, OR of 0.624 (95% CI 0.485-0.802)). This haplotype remained significant after permutation correction (P = 0.0190, s.e. 0.0043; Table 3). More...	Positive
rs2852217 - rs879602 - rs1954787 - rs4935752		GRIK4	P-value = 0.12 between SCZ cases and controls; P-value = 0.041 between all cases and controls		Positive
rs2852217 - rs879602 - rs1954787		GRIK4	P-value = 0.035 between BPD cases and controls; P-value = 0.039 between all cases and controls		Positive
rs948028 - rs2852217		GRIK4	P-value = 0.309 between BPD cases and controls; P-value = 0.383 between all cases and controls		Negative
rs948028 - rs2852217 - rs879602		GRIK4	P-value = 0.011 between BPD cases and controls; P-value = 0.158 between all cases and controls		Positive
rs879602 - rs1954787 - rs4935752		GRIK4	P-value = 0.892 between BPD cases and controls; P-value = 0.449 between all cases and controls		Negative
rs879602 - rs1954787 - rs4935752 - rs6589846		GRIK4	P-value = 0.652 between SCZ cases and controls; P-value = 0.176 between all cases and controls		Negative
rs7928347 - rs2000869 - rs7479743 - rs6589832		GRIK4	P-value = 0.601 between SCZ cases and controls; P-value = 0.306 between all cases and controls		Negative
rs879602 - rs1954787		GRIK4	P-value = 0.885 between BPD cases and controls; P-value = 0.949 between all cases and controls		Negative
rs7928347 - rs2000869		GRIK4	P-value = 0.559 between BPD cases and controls; P-value = 0.583 between all cases and controls		Negative
rs7928347 - rs2000869 - rs7479743		GRIK4	P-value = 0.486 between BPD cases and controls; P-value = 0.43 between all cases and controls		Positive
rs7925270 - rs3133855 - rs3133226		GRIK4	P-value = 0.795 between BPD cases and controls; P-value = 0.876 between all cases and controls		Negative
rs7925270 - rs3133855 - rs3133226 - rs2187495		GRIK4	P-value = 0.544 between SCZ cases and controls; P-value = 0.86 between all cases and controls		Negative
rs7479743 - rs6589832 - rs7925270 - rs3133855	C-G-C-T	GRIK4	P-value = 0.008		Positive
rs7925270 - rs3133855		GRIK4	P-value = 0.768 between BPD cases and controls; P-value = 0.95 between all cases and controls		Negative
rs7479743 - rs6589832 - rs7925270		GRIK4	P-value = 0.239 between BPD cases and controls; P-value = 0.718 between all cases and controls		Positive
rs7479743 - rs6589832 - rs7925270 - rs3133855		GRIK4	P-value = 0.094 between SCZ cases and controls; P-value = 0.712 between all cases and controls		Negative
rs7111184 - rs2156635 - rs949056 - rs949054		GRIK4	P-value = 0.489 between SCZ cases and controls; P-value = 0.271 between all cases and controls		Negative
rs7479743 - rs6589832		GRIK4	P-value = 0.538 between BPD cases and controls; P-value = 0.779 between all cases and controls		Negative
rs7111184 - rs2156635 - rs949056		GRIK4	P-value = 0.486 between BPD cases and controls; P-value = 0.173 between all cases and controls		Negative
rs7111184 - rs2156635		GRIK4	P-value = 0.351 between BPD cases and controls; P-value = 0.277 between all cases and controls		Negative
rs6589846 - rs4430518 - rs433110 - rs7111184		GRIK4	P-value = 0.578 between SCZ cases and controls; P-value = 0.335 between all cases and controls		Negative
rs6589846 - rs4430518 - rs433110		GRIK4	P-value = 0.506 between BPD cases and controls; P-value = 0.34 between all cases and controls		Negative
rs6589846 - rs4430518		GRIK4	P-value = 0.349 between BPD cases and controls; P-value = 0.115 between all cases and controls		Negative
rs6589832 - rs7925270 - rs3133855 - rs3133226	G-C-T-C	GRIK4	P-value = 0.0018, Correction P-value = 0.3187		Positive
rs6589832 - rs7925270 - rs3133855 - rs3133226		GRIK4	P-value = 0.125 between SCZ cases and controls; P-value = 0.831 between all cases and controls		Negative
rs6589832 - rs7925270 - rs3133855	G-C-T	GRIK4	P-value = 0.0018, Correction P-value = 0.2258		Positive
rs6589832 - rs7925270 - rs3133855		GRIK4	P-value = 0.038 between BPD cases and controls; P-value = 0.8 between all cases and controls		Positive
rs6589832 - rs7925270		GRIK4	P-value = 0.48 between BPD cases and controls; P-value = 0.913 between all cases and controls		Negative
rs602104 - rs2276319 - rs513548 - rs2282586	C-A-T-G	GRIK4	P-value = 0.008		Positive
rs602104 - rs2276319 - rs513548 - rs2282586		GRIK4	P-value = 0.136 between SCZ cases and controls; P-value = 0.34 between all cases and controls		Negative
rs602104 - rs2276319 - rs513548		GRIK4	P-value = 0.137 between BPD cases and controls; P-value = 0.314 between all cases and controls		Negative
rs602104 - rs2276319	C-A	GRIK4	P-value = 0.0064		Positive
rs602104 - rs2276319		GRIK4	P-value = 0.056 between BPD cases and controls; P-value = 0.274 between all cases and controls		Negative
rs513548 - rs2282586 - rs1944522	T-G-C	GRIK4	P-value = 0.0021		Positive
rs949056 - rs949054 - rs602104 - rs2276319		GRIK4	P-value = 0.382 between SCZ cases and controls; P-value = 0.91 between all cases and controls		Negative
rs949056 - rs949054 - rs602104	A-T-C	GRIK4	P-value = 0.0043		Positive
rs949056 - rs949054 - rs602104 - rs2276319	A-T-C-A	GRIK4	P-value = 0.0098		Positive
rs949054 - rs602104 - rs2276319 - rs513548		GRIK4	P-value = 0.222 between SCZ cases and controls; P-value = 0.566 between all cases and controls		Negative
rs949054 - rs602104 - rs2276319	T-C-A	GRIK4	P-value = 0.0071		Positive
rs949056 - rs949054 - rs602104		GRIK4	P-value = 0.054 between BPD cases and controls; P-value = 0.364 between all cases and controls		Negative
rs949056 - rs949054		GRIK4	P-value = 0.317 between BPD cases and controls; P-value = 0.767 between all cases and controls		Positive
rs949054 - rs602104		GRIK4	P-value = 0.007 between BPD cases and controls; P-value = 0.093 between all cases and controls		Positive
rs948028 - rs2852217 - rs879602 - rs1954787		GRIK4	P-value = 0.009 between SCZ cases and controls; P-value = 0.005 between all cases and controls		Positive
rs949054 - rs602104 - rs2276319		GRIK4	P-value = 0.124 between BPD cases and controls; P-value = 0.589 between all cases and controls		Negative
rs949054 - rs602104	T-C	GRIK4	P-value = 0.0028		Positive

Genes reported by this study for BD (count: 1)

Gene	Statistical Values/Author Comments	Result Category
GRIK4	Findings of cytogenetic and genetic evidence supported a role for the kainate-type glutamate recepto...... Findings of cytogenetic and genetic evidence supported a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder More...	Positive

Genetic factors reported by this study for SZ and/or MDD

SNPs reported by this study for SZ/MDD

Disease	SNP	Related Gene(s)	Statistical Values	Description	Result Category
SZ	rs949056	GRIK4	P-value = 0.87 between SCZ cases and controls; P-value = 0.476 between all cases and controls		Negative
SZ	rs602104	GRIK4 HMGB1P42	P-value = 0.425 between SCZ cases and controls; P-value = 0.028 between all cases and controls		Positive
SZ	rs513548	GRIK4	P-value = 0.68 between SCZ cases and controls; P-value = 0.786 between all cases and controls		Negative
SZ	rs4935752	GRIK4	P-value = 0.001 between SCZ cases and controls; P-value = 0.022 between all cases and controls; Best global P-value (permutation corrected)=0.03	showed significant association with schizophrenia; SNP 15 remained significantly associated with schizophrenia after permutation analysis to counter multiple testing errors	Positive
SZ	rs4582985	GRIK4	P-value = 0.842 between SCZ cases and controls; P-value = 0.621 between all cases and controls		Negative
SZ	rs4430518	GRIK4	P-value = 0.015 between SCZ cases and controls; P-value = 0.244 between all cases and controls	showed significant association with schizophrenia	Positive
SZ	rs433110	GRIK4	P-value = 0.084 between SCZ cases and controls; P-value = 0.362 between all cases and controls		Negative
SZ	rs4245040	GRIK4	P-value = 0.39 between SCZ cases and controls; P-value = 0.25 between all cases and controls		Negative
SZ	rs3133855	GRIK4	P-value = 0.811 between SCZ cases and controls; P-value = 0.624 between all cases and controls		Negative
SZ	rs949054	GRIK4	P-value = 0.894 between SCZ cases and controls; P-value = 0.509 between all cases and controls		Negative
SZ	rs948028	GRIK4	P-value = 0.504 between SCZ cases and controls; P-value = 0.687 between all cases and controls		Negative
SZ	rs879602	GRIK4	P-value = 0.677 between SCZ cases and controls; P-value = 0.936 between all cases and controls		Negative
SZ	rs7928347	GRIK4	P-value = 0.279 between SCZ cases and controls; P-value = 0.382 between all cases and controls		Negative
SZ	rs7925270	GRIK4	P-value = 0.859 between SCZ cases and controls; P-value = 0.695 between all cases and controls		Negative
SZ	rs7111184	GRIK4	P-value = 0.821 between SCZ cases and controls; P-value = 0.736 between all cases and controls		Negative
SZ	rs6589846	GRIK4	P-value = 0.004 between SCZ cases and controls; P-value = 0.141 between all cases and controls	showed significant association with schizophrenia	Positive
SZ	rs6589832	GRIK4	P-value = 0.6 between SCZ cases and controls; P-value = 0.833 between all cases and controls		Negative
SZ	rs1944522	GRIK4	P-value = 0.842 between SCZ cases and controls; P-value = 0.405 between all cases and controls		Negative
SZ	rs1954787	GRIK4	P-value = 0.472 between SCZ cases and controls; P-value = 0.515 between all cases and controls		Negative
SZ	rs3132780	GRIK4	P-value = 0.464 between SCZ cases and controls; P-value = 0.514 between all cases and controls		Negative
SZ	rs3133226	GRIK4	P-value = 0.806 between SCZ cases and controls; P-value = 0.904 between all cases and controls		Negative
SZ	rs2282586	GRIK4	P-value = 0.358 between SCZ cases and controls; P-value = 0.058 between all cases and controls		Negative
SZ	rs2852217	GRIK4	P-value = 0.405 between SCZ cases and controls; P-value = 0.175 between all cases and controls		Negative
SZ	rs2187495	GRIK4	P-value = 0.864 between SCZ cases and controls; P-value = 0.357 between all cases and controls		Negative
SZ	rs2276319	GRIK4	P-value = 0.94 between SCZ cases and controls; P-value = 0.675 between all cases and controls		Negative
SZ	rs2000869	GRIK4	P-value = 0.984 between SCZ cases and controls; P-value = 0.677 between all cases and controls		Negative
SZ	rs2156635	GRIK4	P-value = 0.081 between SCZ cases and controls; P-value = 0.041 between all cases and controls		Positive

Haplotypes reported by this study for SZ/MDD

Disease	Markers	Related Gene(s)/Region(s)	Statistical Values	Description	Result Category
SZ	rs2852217 - rs879602 - rs1954787 - rs4935752	GRIK4	P-value = 0.006 between SCZ cases and controls; P-value = 0.041 between all cases and controls		Positive
SZ	rs2852217 - rs879602 - rs1954787	GRIK4	P-value = 0.03 between SCZ cases and controls; P-value = 0.039 between all cases and controls		Positive
SZ	rs3132780 - rs948028 - rs2852217	GRIK4	P-value = 0.696 between SCZ cases and controls; P-value = 0.543 between all cases and controls		Negative
SZ	rs3132780 - rs948028	GRIK4	P-value = 0.619 between SCZ cases and controls; P-value = 0.779 between all cases and controls		Negative
SZ	rs3133226 - rs2187495	GRIK4	P-value = 0.98 between SCZ cases and controls; P-value = 0.492 between all cases and controls		Negative
SZ	rs3132780 - rs948028 - rs2852217 - rs879602	GRIK4	P-value = 0.905 between SCZ cases and controls; P-value = 0.171 between all cases and controls		Negative
SZ	rs3133226 - rs2187495 - rs3132780 - rs948028	GRIK4	P-value = 0.767 between SCZ cases and controls; P-value = 0.597 between all cases and controls		Negative
SZ	rs3133226 - rs2187495 - rs3132780	GRIK4	P-value = 0.84 between SCZ cases and controls; P-value = 0.564 between all cases and controls		Negative
SZ	rs2187495 - rs3132780 - rs948028	GRIK4	P-value = 0.713 between SCZ cases and controls; P-value = 0.508 between all cases and controls		Negative
SZ	rs2187495 - rs3132780	GRIK4	P-value = 0.819 between SCZ cases and controls; P-value = 0.495 between all cases and controls		Negative
SZ	rs2276319 - rs513548	GRIK4	P-value = 0.643 between SCZ cases and controls; P-value = 0.472 between all cases and controls		Negative
SZ	rs2187495 - rs3132780 - rs948028 - rs2852217	GRIK4	P-value = 0.827 between SCZ cases and controls; P-value = 0.774 between all cases and controls		Negative
SZ	rs2276319 - rs513548 - rs2282586 - rs1944522	GRIK4	P-value = 0.781 between SCZ cases and controls; P-value = 0.113 between all cases and controls		Negative
SZ	rs2276319 - rs513548 - rs2282586	GRIK4	P-value = 0.496 between SCZ cases and controls; P-value = 0.186 between all cases and controls		Negative
SZ	rs2852217 - rs879602	GRIK4	P-value = 0.825 between SCZ cases and controls; P-value = 0.232 between all cases and controls		Negative
SZ	rs2282586 - rs1944522	GRIK4	P-value = 0.708 between SCZ cases and controls; P-value = 0.048 between all cases and controls		Positive
SZ	rs433110 - rs7111184 - rs2156635 - rs949056	GRIK4	P-value = 0.305 between SCZ cases and controls; P-value = 0.707 between all cases and controls		Negative
SZ	rs4430518 - rs433110	GRIK4	P-value = 0.14 between SCZ cases and controls; P-value = 0.769 between all cases and controls		Negative
SZ	rs4430518 - rs433110 - rs7111184	GRIK4	P-value = 0.135 between SCZ cases and controls; P-value = 0.855 between all cases and controls		Negative
SZ	rs4430518 - rs433110 - rs7111184 - rs2156635	GRIK4	P-value = 0.367 between SCZ cases and controls; P-value = 0.758 between all cases and controls		Negative
SZ	rs4935752 - rs6589846	GRIK4	P-value = 0.005 between SCZ cases and controls; P-value = 0.103 between all cases and controls	These positionally bi-partite findings were further supported by a sliding window global analysis of haplotypes of lengths two to four, such that distinct clusters of significant P-values were observed in schizophrenia (best global haplotype, SNPs 15 and 16; P = 0.005).	Positive
SZ	rs4935752 - rs6589846 - rs4430518	GRIK4	P-value = 0.015 between SCZ cases and controls; P-value = 0.16 between all cases and controls		Positive
SZ	rs4935752 - rs6589846 - rs4430518 - rs433110	GRIK4	P-value = 0.016 between SCZ cases and controls; P-value = 0.128 between all cases and controls		Positive
SZ	rs513548 - rs2282586	GRIK4	P-value = 0.288 between SCZ cases and controls; P-value = 0.093 between all cases and controls		Negative
SZ	rs3133855 - rs3133226	GRIK4	P-value = 0.985 between SCZ cases and controls; P-value = 0.971 between all cases and controls		Negative
SZ	rs3133855 - rs3133226 - rs2187495	GRIK4	P-value = 0.999 between SCZ cases and controls; P-value = 0.885 between all cases and controls		Negative
SZ	rs3133855 - rs3133226 - rs2187495 - rs3132780	GRIK4	P-value = 0.965 between SCZ cases and controls; P-value = 0.824 between all cases and controls		Negative
SZ	rs4245040 - rs7928347	GRIK4	P-value = 0.364 between SCZ cases and controls; P-value = 0.089 between all cases and controls		Negative
SZ	rs4245040 - rs7928347 - rs2000869	GRIK4	P-value = 0.704 between SCZ cases and controls; P-value = 0.288 between all cases and controls		Negative
SZ	rs4245040 - rs7928347 - rs2000869 - rs7479743	GRIK4	P-value = 0.484 between SCZ cases and controls; P-value = 0.221 between all cases and controls		Negative
SZ	rs433110 - rs7111184	GRIK4	P-value = 0.149 between SCZ cases and controls; P-value = 0.606 between all cases and controls		Negative
SZ	rs433110 - rs7111184 - rs2156635	GRIK4	P-value = 0.419 between SCZ cases and controls; P-value = 0.57 between all cases and controls		Negative
SZ	rs7111184 - rs2156635 - rs949056	GRIK4	P-value = 0.045 between SCZ cases and controls; P-value = 0.173 between all cases and controls		Positive
SZ	rs7111184 - rs2156635	GRIK4	P-value = 0.363 between SCZ cases and controls; P-value = 0.277 between all cases and controls		Negative
SZ	rs6589846 - rs4430518 - rs433110 - rs7111184	GRIK4	P-value = 0.055 between SCZ cases and controls; P-value = 0.335 between all cases and controls		Negative
SZ	rs6589846 - rs4430518 - rs433110	GRIK4	P-value = 0.059 between SCZ cases and controls; P-value = 0.34 between all cases and controls		Negative
SZ	rs7479743 - rs6589832 - rs7925270 - rs3133855	GRIK4	P-value = 0.757 between SCZ cases and controls; P-value = 0.712 between all cases and controls		Negative
SZ	rs7479743 - rs6589832 - rs7925270	GRIK4	P-value = 0.597 between SCZ cases and controls; P-value = 0.718 between all cases and controls		Negative
SZ	rs7479743 - rs6589832	GRIK4	P-value = 0.87 between SCZ cases and controls; P-value = 0.779 between all cases and controls		Negative
SZ	rs7111184 - rs2156635 - rs949056 - rs949054	GRIK4	P-value = 0.118 between SCZ cases and controls; P-value = 0.271 between all cases and controls		Negative
SZ	rs602104 - rs2276319 - rs513548 - rs2282586	GRIK4	P-value = 0.695 between SCZ cases and controls; P-value = 0.34 between all cases and controls		Negative
SZ	rs602104 - rs2276319 - rs513548	GRIK4	P-value = 0.781 between SCZ cases and controls; P-value = 0.314 between all cases and controls		Negative
SZ	rs602104 - rs2276319	GRIK4	P-value = 0.908 between SCZ cases and controls; P-value = 0.274 between all cases and controls		Negative
SZ	rs513548 - rs2282586 - rs1944522	GRIK4	P-value = 0.41 between SCZ cases and controls; P-value = 0.054 between all cases and controls		Negative
SZ	rs6589846 - rs4430518	GRIK4	P-value = 0.007 between SCZ cases and controls; P-value = 0.115 between all cases and controls		Positive
SZ	rs6589832 - rs7925270 - rs3133855 - rs3133226	GRIK4	P-value = 0.833 between SCZ cases and controls; P-value = 0.831 between all cases and controls		Negative
SZ	rs6589832 - rs7925270 - rs3133855	GRIK4	P-value = 0.837 between SCZ cases and controls; P-value = 0.8 between all cases and controls		Negative
SZ	rs6589832 - rs7925270	GRIK4	P-value = 0.474 between SCZ cases and controls; P-value = 0.913 between all cases and controls		Negative
SZ	rs948028 - rs2852217 - rs879602	GRIK4	P-value = 0.938 between SCZ cases and controls; P-value = 0.158 between all cases and controls		Negative
SZ	rs948028 - rs2852217 - rs879602 - rs1954787	GRIK4	P-value = 0.043 between SCZ cases and controls; P-value = 0.005 between all cases and controls		Positive
SZ	rs879602 - rs1954787 - rs4935752 - rs6589846	GRIK4	P-value = 0.028 between SCZ cases and controls; P-value = 0.176 between all cases and controls		Positive
SZ	rs948028 - rs2852217	GRIK4	P-value = 0.598 between SCZ cases and controls; P-value = 0.383 between all cases and controls		Negative
SZ	rs949054 - rs602104 - rs2276319 - rs513548	GRIK4	P-value = 0.945 between SCZ cases and controls; P-value = 0.566 between all cases and controls		Negative
SZ	rs949056 - rs949054	GRIK4	P-value = 0.972 between SCZ cases and controls; P-value = 0.767 between all cases and controls		Negative
SZ	rs949054 - rs602104	GRIK4	P-value = 0.769 between SCZ cases and controls; P-value = 0.093 between all cases and controls		Negative
SZ	rs949054 - rs602104 - rs2276319	GRIK4	P-value = 0.99 between SCZ cases and controls; P-value = 0.589 between all cases and controls		Negative
SZ	rs7925270 - rs3133855 - rs3133226 - rs2187495	GRIK4	P-value = 0.984 between SCZ cases and controls; P-value = 0.86 between all cases and controls		Negative
SZ	rs7928347 - rs2000869	GRIK4	P-value = 0.735 between SCZ cases and controls; P-value = 0.583 between all cases and controls		Negative
SZ	rs7925270 - rs3133855	GRIK4	P-value = 0.952 between SCZ cases and controls; P-value = 0.95 between all cases and controls		Negative
SZ	rs7925270 - rs3133855 - rs3133226	GRIK4	P-value = 0.886 between SCZ cases and controls; P-value = 0.876 between all cases and controls		Negative
SZ	rs879602 - rs1954787	GRIK4	P-value = 0.702 between SCZ cases and controls; P-value = 0.949 between all cases and controls		Negative
SZ	rs879602 - rs1954787 - rs4935752	GRIK4	P-value = 0.067 between SCZ cases and controls; P-value = 0.449 between all cases and controls		Negative
SZ	rs7928347 - rs2000869 - rs7479743	GRIK4	P-value = 0.612 between SCZ cases and controls; P-value = 0.43 between all cases and controls		Negative
SZ	rs7928347 - rs2000869 - rs7479743 - rs6589832	GRIK4	P-value = 0.187 between SCZ cases and controls; P-value = 0.306 between all cases and controls		Negative
SZ	rs949056 - rs949054 - rs602104 - rs2276319	GRIK4	P-value = 0.997 between SCZ cases and controls; P-value = 0.91 between all cases and controls		Negative
SZ	rs949056 - rs949054 - rs602104	GRIK4	P-value = 0.931 between SCZ cases and controls; P-value = 0.364 between all cases and controls		Negative
SZ	rs1954787 - rs4935752	GRIK4	P-value = 0.008 between SCZ cases and controls; P-value = 0.088 between all cases and controls		Positive
SZ	rs2156635 - rs949056 - rs949054 - rs602104	GRIK4	P-value = 0.091 between SCZ cases and controls; P-value = 0.117 between all cases and controls		Negative
SZ	rs2156635 - rs949056 - rs949054	GRIK4	P-value = 0.04 between SCZ cases and controls; P-value = 0.129 between all cases and controls		Positive
SZ	rs2156635 - rs949056	GRIK4	P-value = 0.004 between SCZ cases and controls; P-value = 0.027 between all cases and controls		Positive
SZ	rs2000869 - rs7479743 - rs6589832 - rs7925270	GRIK4	P-value = 0.365 between SCZ cases and controls; P-value = 0.483 between all cases and controls		Negative
SZ	rs2000869 - rs7479743 - rs6589832	GRIK4	P-value = 0.466 between SCZ cases and controls; P-value = 0.391 between all cases and controls		Negative
SZ	rs2000869 - rs7479743	GRIK4	P-value = 0.538 between SCZ cases and controls; P-value = 0.448 between all cases and controls		Negative
SZ	rs1954787 - rs4935752 - rs6589846 - rs4430518	GRIK4	P-value = 0.068 between SCZ cases and controls; P-value = 0.32 between all cases and controls		Negative
SZ	rs1954787 - rs4935752 - rs6589846	GRIK4	P-value = 0.024 between SCZ cases and controls; P-value = 0.287 between all cases and controls		Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	GRIK4	Findings of cytogenetic and genetic evidence supported a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder	Positive