GENETIC MARKERS OF MENTAL ILLNESS

• US 20100279423A1
• Filed: 01/02/2009
• Published: 11/04/2010
• Est. Priority Date: 01/02/2008
• Status: Abandoned Application

• Current Assignee: SureGene, LLC
• Original Assignee: SureGene, LLC
• Inventors: Ramsey, Timothy Lynn, Brennan, Mark David
• Application Number:
  US12/523,252
• Publication Number:
  US 20100279423A1
• Time in Patent Office: Days
• US Class Current: 436/94
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

This invention relates to genetic markers of mental illness, e.g., schizophrenia (SZ) and methods of use thereof.

Claims

1. A method of determining a human subject'"'"'s risk of developing schizophrenia (SZ), the method comprising:

obtaining a test haplotype for the subject by determining the genotype of at least one test marker listed in Table B, or a test marker that lies between a pair of delimiting markers listed in Table A and that is in linkage disequilibrium with markers listed in Table B,

wherein the test haplotype indicates the subject'"'"'s risk of developing SZ.

2. The method of claim 1, wherein the at least one test marker is in a neuronal cell adhesion molecule (NRCAM) gene or an intraflagellar transport 57 homolog (Chlamydomonas) (IFT57) gene, and further is selected from the group consisting of:

rs11983886;

rs441468;

rs411444;

rs439587;

rs12670313;

rs12537654;

rs2142325;

rs401433;

rs409797;

rs428459;

rs6962066;

rs381318;

rs381318;

rs409797;

rs411444;

rs428459;

rs439587;

rs441468;

rs6958498;

rs12670313;

rs401433;

rs404287;

rs2142325;

rs6962066;

rs12537654;

rs404287;

rs6958498;

rs326335; and

rs16854283;

or is a test marker in LD with these markers;

wherein the genotype of the test marker indicates the subject'"'"'s risk of developing SZ

3. The method of claim 1, wherein the at least one test marker is are selected from the group consisting of:

rs1198849;

rs6736116;

rs2302941;

rs7584861;

rs4668892;

rs3805095;

rs1615739;

rs4853516;

rs2293765;

rs1168;

rs984610;

rs2204859;

rs10170881;

rs10187928;

rs4311010;

rs4456647;

rs1801251;

rs11681604;

rs6759206;

rs2278884;

rs11899677;

rs2304725;

rs4684739;

rs2245532;

rs2272395;

rs4298061;

rs4298061;

rs9875169;

rs9835094;

rs6807382;

rs7645021;

rs10804442;

rs13060223;

rs1289766;

rs428321;

rs326335;

rs16854283;

rs1289750;

rs1289754;

rs3749309;

rs725981;

rs6822297;

rs6855865;

rs10939141;

rs3762900;

rs1012550;

rs13139479;

rs13151864;

rs7653897;

rs17023119;

rs1032138;

rs10856914;

rs3804350;

rs1405686;

rs6532920;

rs6812406;

rs2905990;

rs2905990;

rs1990005;

rs2158444;

rs32264;

rs258630;

rs258630;

rs258634;

rs6875838;

rs249264;

rs1458472;

rs2168879;

rs6453217;

rs10066037;

rs4530741;

rs16875377;

rs1046819;

rs4143069;

rs11950060;

rs10076542;

rs906362;

rs4242157;

rs6879997;

rs11134732;

rs2079460;

rs6966154;

rs2357958;

rs3823843;

rs4721345;

rs3823843;

rs4721345;

rs979499;

rs4632953;

rs4632953;

rs979499;

rs6461275;

rs2290837;

rs3807509;

rs4721539;

rs7808455;

rs6961002;

rs12536620;

rs12667819;

rs1526083;

rs11983886;

rs11983886;

rs441468;

rs411444;

rs439587;

rs12670313;

rs12537654;

rs2142325;

rs401433;

rs409797;

rs428459;

rs6962066;

rs381318;

rs381318;

rs409797;

rs411444;

rs428459;

rs439587;

rs441468;

rs6958498;

rs12670313;

rs401433;

rs404287;

rs2142325;

rs6962066;

rs12537654;

rs404287;

rs6958498;

rs7463766;

rs12541005;

rs9987318;

rs11167136;

rs4325020;

rs12547214;

rs6583623;

rs7462663;

rs3808493;

rs4574919;

rs12555560;

rs16916080;

rs16916080;

rs7864467;

rs10981815;

rs12338788;

rs12351728;

rs1001506;

rs4979387;

rs731421;

rs2274158;

rs10759694;

rs10982256;

rs11790014;

rs10513278;

rs10983437;

rs1888288;

rs10983437;

rs4838143;

rs4838143;

rs6481183;

rs2251601;

rs1937655;

rs1937672;

rs7083967;

rs11001472;

rs13499;

rs1881597;

rs3812658;

rs857395;

rs721825;

rs7093302;

rs2153822;

rs11004439;

rs1911342;

rs7092601;

rs2147886;

rs2894028;

rs10822960;

rs12265366;

rs7448;

rs927639;

rs3748234;

rs10736114;

rs11188853;

rs3748236;

rs11188844;

rs12784975;

rs563654;

rs3748229;

rs7922865; and

rs2817667;

or is a test markers in LD with one of these markers;

wherein the genotype of the test marker indicates the subject'"'"'s risk of developing SZ.

24. The method of claim 1, wherein the test haplotype indicates that the subject has an increased risk of developing SZ.

25. The method of claim 1, wherein obtaining a test haplotype comprises:

obtaining a sample comprising DNA from the subject; and

determining the genotype for the test marker.

26. The method of claim 1, further comprising:

obtaining a reference haplotype comprising a reference marker that corresponds to the test marker; and

comparing the test haplotype to the reference haplotype, wherein the presence of a haplotype in both the test haplotype and a reference haplotype is indicative of likelihood that a subject will develop SZ, likely pharmacological response, or likely severity of a psychiatric endophenotype.

27. The method of claim 26, wherein the reference haplotype is from one or more subjects who have SZ and the presence of a haplotype in both the test haplotype and the reference haplotype indicates that there is an increased likelihood that the subject will develop SZ.

28. The method of claim 26, wherein the reference haplotype comprises a haplotype from at least one of the following relatives of the subject:

(a) a parent who has SZ, SD, or SPD;

(b) a sibling who has SZ, SD, or SPD, and an unaffected parent;

or

(c) a second degree relative who has SZ, SD, or SPD and an unaffected parent;

wherein sharing of a haplotype between the test haplotype and the reference haplotype from the relative who has SZ, SD, or SPD, is indicative of an increased likelihood that the subject will develop broadly defined SZ.

29. The method of claim 1, further comprising determining the genotype of one or more additional markers listed in Table B, or one or more test markers that are in linkage disequilibrium with a marker listed in Table B.

30. The method of claim 1, wherein the subject is a patient having or suspected of having SZ.

31. The method of claim 1, wherein the subject has one or more risk factors associated with SZ.

32. The method of claim 31, wherein the risk factors associated with SZ or BD include one or more of:

a relative afflicted with SZ, SPD, SD or Bipolar Disorder; and

a genetically based phenotypic trait associated with risk for SZ, SPD, or SD.

33. The method of claim 1, further comprising selecting or excluding a subject for enrollment in a clinical trial based on the test haplotype.

34. The method of claim 1, further comprising stratifying a subject population for analysis of a clinical trial based on test haplotypes in the subjects.

35. The method of claim 1, further comprising confirming a diagnosis of SZ using psychometric instruments.

36. The method of claim 1, further comprising stratifying patients into biologically similar groups based on test haplotypes in order to determine a differential diagnosis.

46. The method of claim 1, wherein obtaining a test haplotype comprises obtaining a sample comprising genomic DNA of the subject, and determining the identity of the alleles at the test markers.

47. The method of claim 1, wherein obtaining a test haplotype comprises constructing a haplotype using previously determined genotype information, wherein the previously determined genotype information includes at least one test marker that is listed in Table B or is in linkage disequilibrium with a marker listed in Table B.

4. A method of predicting a human subject'"'"'s likely response to an antipsychotic medication, the method comprising:

obtaining a test haplotype for the subject by determining the genotype for at least one test marker listed in Table B, or at least one test marker that lies between the delimiting markers in Table A and that is in linkage disequilibrium (LD) with a marker listed in Table B,

wherein the test haplotype indicates the subject'"'"'s likely response to an antipsychotic medication.

5. The method of claim 4, wherein the treatment is administration of olanzapine, and the at least one test marker is in a gene selected from the group consisting of pregnancy-associated plasma protein A, pappalysin 1 (PAPPA), peptidylprolyl isomerase domain and WD repeat containing 1 (PPWD1), inositol polyphosphate-1-phosphatase (INPP1), and unc-5 homolog C (C. elegans) (UNC5C), and further is selected from the group consisting of rs1405;

rs405485;

rs407200;

rs1888636;

rs10817865;

rs10983070;

rs10983085;

rs13290387;

rs669571;

rs27139;

rs4656;

rs2016037;

rs10931450;

rs7592352 ; and

rs4699415;

or is a test markers in LD with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of olanzapine.

6. The method of claim 4, wherein the treatment is administration of olanzapine, and the at least one test marker is selected from the group consisting of:

rs1011919;

rs1012550;

rs10186418;

rs10516092;

rs10517369;

rs1054402;

rs10817865;

rs10822960;

rs10931450;

rs10939141;

rs10942768;

rs10983070;

rs10983085;

rs11001472;

rs11188985;

rs1159653;

rs12505322;

rs12642020;

rs12651329;

rs12692275;

rs13029846;

rs13139479;

rs13151864;

rs13290387;

rs1405;

rs154858;

rs154859;

rs15963;

rs1608890;

rs16991904;

rs1878825;

rs1888636;

rs1925570;

rs1940251;

rs2016037;

rs2111007;

rs2147886;

rs2248213;

rs2271810;

rs2276322;

rs2569091;

rs27139;

rs2894028;

rs2905990;

rs353119;

rs3733212;

rs37337;

rs37338;

rs3747516;

rs3748229;

rs3762900;

rs405485;

rs407200;

rs41353;

rs42468;

rs4298061;

rs432206;

rs4403715;

rs461534;

rs4618168;

rs4656;

rs4663999;

rs4668888;

rs4668909;

rs468754;

rs468821;

rs4699415;

rs4699836;

rs4746659;

rs4853561;

rs4853581;

rs4858798;

rs4858828;

rs4858831;

rs4935502;

rs6453217;

rs6532920;

rs6555980;

rs6555982;

rs6555988;

rs669571;

rs6730450;

rs6812406;

rs6822297;

rs6851143;

rs6855865;

rs6875838;

rs6951528;

rs702110;

rs706713;

rs7083967;

rs7093302;

rs725981;

rs7462663;

rs7518;

rs7592352;

rs7922865;

rs839282;

rs857395;

rs915281;

rs983513; and

rs9998217;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of olanzapine.

7. The method of claim 4, wherein the treatment is administration of risperidone, and the at least one test marker is in a gene selected from the group consisting of roundabout, axon guidance receptor, homolog 1 (Drosophila) (ROBO1), solute carrier family 4, sodium bicarbonate transporter, member 10 (SLC4A10), astrotactin 2 (ASTN2), or protocadherin 15 (PCDH15), and further is selected from the group consisting of:

rs3773190;

rs11925452 ;

rs1372332;

rs4519000;

rs10825169;

rs2921922;

rs1900438;

rs10825150;

rs17644321;

rs11004028; and

rs12617656;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of risperidone.

8. The method of claim 4, wherein the treatment is administration of risperidone, and the at least one test marker is selected from the group consisting of:

rs1001506;

rs10033209;

rs1007722;

rs10077289;

rs10166174;

rs10255136;

rs1027833;

rs10435873;

rs1054750;

rs10733833;

rs10760348;

rs10804442;

rs10822960;

rs10825113;

rs10825150;

rs10825169;

rs10856914;

rs11001472;

rs11004028;

rs11097378;

rs11167136;

rs11925452;

rs1232514;

rs12547214;

rs12555560;

rs12617656;

rs12642922;

rs12646356;

rs12692275;

rs1289750;

rs1289754;

rs1289766;

rs13029846;

rs13060223;

rs13094;

rs13130069;

rs13132085;

rs1323438;

rs1351999;

rs1372332;

rs1531111;

rs16850532;

rs16854283;

rs17644321;

rs17662644;

rs1821223;

rs1900438;

rs1905717;

rs1913808;

rs1925610;

rs1937672;

rs1978516;

rs2042145;

rs2049625;

rs2065221;

rs2105702;

rs2147886;

rs2215173;

rs2248213;

rs2248465;

rs2251601;

rs2254485;

rs2274780;

rs2277054;

rs2286282;

rs2302179;

rs2339953;

rs2416;

rs2431363;

rs2518100;

rs2701685;

rs2732509;

rs2894028;

rs2921922;

rs2924307;

rs314155;

rs326335;

rs353119;

rs3739709;

rs3755851;

rs3773190;

rs3773202;

rs3775433;

rs428321;

rs4325020;

rs4519000;

rs462307;

rs4632953;

rs464049;

rs4668909;

rs4832524;

rs4858798;

rs4858828;

rs4858831;

rs491855;

rs4973588;

rs4979387;

rs498328;

rs6432706;

rs6481183;

rs6713395;

rs6807382;

rs6951528;

rs7020782;

rs7038903;

rs7083967;

rs716386;

rs7355529;

rs7518;

rs7577213;

rs7592352;

rs7632502;

rs7645021;

rs7649466;

rs7852962;

rs7863519;

rs872665;

rs944333; and

rs979499;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of risperidone.

9. The method of claim 4, wherein the treatment is administration of quetiapine, and the at least one test marker is in a gene selected from the group consisting of catenin (cadherin-associated protein), alpha 3 (CTNNA3), potassium inwardly-rectifying channel, subfamily J, member 13 (KCNJ13), zinc finger protein 659 (ZNF659), and sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1), and further is selected from the group consisting of:

rs10762170;

rs10822976;

rs12265366;

rs1925570;

rs2147886;

rs2894028;

rs4746659;

rs7074696;

rs1801251;

rs2054942; and

rs7038903;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of quetiapine.

10. The method of claim 4, wherein the one or more test markers is selected from the group consisting of:

rs10049102;

rs10189040;

rs10255136;

rs10264427;

rs1027833;

rs1046819;

rs1047855;

rs10517369;

rs1060962;

rs10762170;

rs10786368;

rs10803666;

rs10822976;

rs10825269;

rs10866692;

rs10931450;

rs10942856;

rs10995555;

rs10997677;

rs11004439;

rs11097378;

rs11925452;

rs11983886;

rs12265366;

rs12355844;

rs12522368;

rs12642922;

rs12651329;

rs12670550;

rs13132085;

rs13166213;

rs13236767;

rs1366116;

rs1385405;

rs1393098;

rs1458472;

rs1468684;

rs1525088;

rs16862653;

rs16875377;

rs16991904;

rs1734436;

rs1801251;

rs1878825;

rs1925570;

rs1965629;

rs2005557;

rs2016037;

rs2052029;

rs2054942;

rs2092996;

rs2147886;

rs2153822;

rs2215173;

rs2248465;

rs2269920;

rs2271151;

rs2271810;

rs2300053;

rs2304725;

rs2305522;

rs2339628;

rs2357958;

rs249264;

rs2530910;

rs2701685;

rs2727591;

rs2817693;

rs2842103;

rs2894028;

rs2900131;

rs3733398;

rs3740292;

rs3755851;

rs3773190;

rs3773202;

rs3796675;

rs3805095;

rs3818876;

rs3823843;

rs3922654;

rs4077871;

rs4530741;

rs4632953;

rs4656;

rs4668892;

rs4684739;

rs4721345;

rs4746659;

rs4917784;

rs563654;

rs6431648;

rs6555913;

rs6711120;

rs6736116;

rs6788511;

rs6795556;

rs6822297;

rs6875838;

rs6879997;

rs6951528;

rs7038903;

rs7074696;

rs716386;

rs725981;

rs726471;

rs735368;

rs749585;

rs7584861;

rs7648952;

rs7659075;

rs7839244;

rs7852962;

rs7863519;

rs944333;

rs975302;

rs978588;

rs979499;

rs9817233;

rs9841335; and

rs9942691;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of quetiapine.

11. The method of claim 4, wherein the treatment is administration of perphenazine, and the at least one test marker is in a gene selected from the group consisting of neuromedin U receptor 1 (NMUR1), IQ motif containing GTPase activating protein 2 (IQGAP2), and EPH receptor A3 (EPHA3), and further is selected from the group consisting of:

rs10933376;

rs7722711;

rs6453217 ;

rs6453217;

rs9835094;

rs13074291; and

rs7646842;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to perphenazine.

12. The method of claim 4, wherein the treatment is administration of perphenazine, and the at least one test marker is selected from the group consisting of:

rs10004009;

rs10180365;

rs10255136;

rs1036111;

rs1042852;

rs10760348;

rs10817881;

rs10933376;

rs10997677;

rs11128704;

rs11790014;

rs12522368;

rs12541005;

rs12642020;

rs1289766;

rs13060223;

rs13074291;

rs13130069;

rs13139479;

rs13151864;

rs13157965;

rs13166213;

rs13316876;

rs1346946;

rs1352889;

rs1366116;

rs1406218;

rs1458472;

rs1468684;

rs1507909;

rs1531111;

rs1615739;

rs16838658;

rs16854283;

rs17515800;

rs1997040;

rs2052029;

rs2054942;

rs2065221;

rs2090700;

rs2135720;

rs2139506;

rs2158444;

rs2168879;

rs2248465;

rs2250861;

rs2251238;

rs2254485;

rs2274780;

rs2276322;

rs2290837;

rs2293339;

rs2293353;

rs2302827;

rs2302941;

rs2356757;

rs2356945;

rs2416;

rs2701685;

rs2817662;

rs2817693;

rs2851060;

rs2905990;

rs2972336;

rs3214046;

rs326335;

rs3733212;

rs3733952;

rs376703;

rs3796403;

rs3805095;

rs3807218;

rs3807509;

rs3822290;

rs4242157;

rs428321;

rs4298061;

rs4374690;

rs4632953;

rs4668892;

rs4699415;

rs4699836;

rs4837498;

rs6446489;

rs6453217;

rs6461275;

rs6532920;

rs6736116;

rs6851143;

rs6860508;

rs7047593;

rs7463766;

rs754750;

rs7584861;

rs759656;

rs7620516;

rs7646842;

rs7657032;

rs7722711;

rs7808455;

rs849412;

rs885725;

rs906362;

rs919615;

rs944333;

rs9639213;

rs9651326;

rs979499;

rs9835094;

rs984576; and

rs9987318;

or is a test markers that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of perphenazine.

13. The method of claim 4, wherein the treatment is administration of ziprasidone, and the at least one test marker is in a gene selected from the group consisting of HCLS1 binding protein 3 (HS1BP3), HMP19 protein (HMP19), and phosphodiesterase 8B (PDE8B);

and is further selected from the group consisting of;

rs4666449;

rs10166174;

rs3811980;

rs4457100; and

rs11953611;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of ziprasidone.

14. The method of claim 4, wherein the treatment is administration of ziprasidone, and the at least one test marker is selected from the group consisting of:

rs10011755;

rs10166174;

rs1027833;

rs1047855;

rs10517369;

rs10739412;

rs10759694;

rs10762168;

rs10762170;

rs10786368;

rs10817025;

rs10822960;

rs10822976;

rs10825113;

rs10825150;

rs10825169;

rs10942768;

rs10983437;

rs10995555;

rs11004028;

rs11188844;

rs1159653;

rs11769313;

rs11953611;

rs1232515;

rs12339210;

rs12505322;

rs12642922;

rs12651095;

rs12651329;

rs12784975;

rs13006199;

rs1323438;

rs13236767;

rs1408524;

rs1449629;

rs1476123;

rs16916091;

rs16991904;

rs17644321;

rs1878825;

rs1900438;

rs1911490;

rs1925570;

rs1937655;

rs2031665;

rs2072546;

rs2147886;

rs2271810;

rs2273977;

rs2274158;

rs2274159;

rs2289914;

rs2297524;

rs2302941;

rs2305522;

rs2316533;

rs2581754;

rs2817662;

rs2817667;

rs2850359;

rs2894028;

rs2921922;

rs314155;

rs3748236;

rs3754659;

rs3768703;

rs3773202;

rs3804775;

rs3805095;

rs3811980;

rs3818876;

rs3823843;

rs3823957;

rs4374690;

rs4457100;

rs4574919;

rs4632953;

rs4666449;

rs4668892;

rs4721345;

rs4746659;

rs4853561;

rs4853581;

rs4858014;

rs4917784;

rs4960617;

rs4978584;

rs573092;

rs6320;

rs6446469;

rs6453217;

rs6736116;

rs6822297;

rs6875838;

rs6970857;

rs7020782;

rs7030830;

rs7047593;

rs716386;

rs725981;

rs731421;

rs7355529;

rs7432676;

rs748741;

rs7559293;

rs7577213;

rs7584861;

rs7626143;

rs7648952;

rs7839244;

rs7903280;

rs9299198;

rs942519;

rs9651326;

rs979499;

rs9817233;

rs983513;

rs9841335;

rs9942691;

rs9993666; and

rs9998217;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of ziprasidone.

15. The method of claim 4, wherein the treatment is administration of an antipsychotic drug, and the at least one test marker is in a gene selected from the group consisting of neuroblastoma-amplified protein (NAG), NIMA (never in mitosis gene a)-related kinase 6 (NEK6), serine/threonine kinase 10 (STK10), and phosphoinositide-3-kinase adaptor protein 1(PIK3AP1), and is further selected from the group consisting of:

rs2302941;

rs4668909;

rs13029846;

rs12692275;

rs2065221;

rs10760348;

rs748741;

rs563654; and

rs11134732;

or is a test markers that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of an antipsychotic.

16. The method of claim 4, wherein the treatment is administration of an antipsychotic, and the at least one test marker is selected from the group consisting of:

rs10086550;

rs10166174;

rs10180365;

rs1036111;

rs1047855;

rs10517369;

rs1060962;

rs10760348;

rs10762168;

rs10762170;

rs10856914;

rs10931450;

rs10942768;

rs10942856;

rs10982256;

rs11097378;

rs11134732;

rs11167136;

rs1159653;

rs11983886;

rs12265366;

rs12355844;

rs12537654;

rs12555560;

rs12642922;

rs12651329;

rs12670313;

rs12673675;

rs12692275;

rs13029846;

rs13094;

rs13236767;

rs13316876;

rs1346946;

rs1372332;

rs1406218;

rs1458472;

rs1468684;

rs1514326;

rs1531111;

rs1608890;

rs16991904;

rs17662644;

rs1878825;

rs2005557;

rs2016037;

rs2052029;

rs2065221;

rs2142325;

rs2248465;

rs2251601;

rs2271810;

rs2274159;

rs2289914;

rs2300053;

rs2302941;

rs2305522;

rs2339628;

rs2357958;

rs2701685;

rs2817667;

rs2905990;

rs314155;

rs3739709;

rs3774883;

rs3775433;

rs381318;

rs3815252;

rs3821936;

rs3823843;

rs3922654;

rs401433;

rs404287;

rs40847;

rs40849;

rs40877;

rs40893;

rs409797;

rs411444;

rs4242157;

rs428459;

rs4374690;

rs439587;

rs441468;

rs4519000;

rs4632953;

rs4656;

rs4668909;

rs4721345;

rs4853561;

rs4853581;

rs491855;

rs4960617;

rs498328;

rs563654;

rs6446469;

rs6453217;

rs6532920;

rs6875838;

rs6958498;

rs6962066;

rs7009759;

rs7038903;

rs726471;

rs7355529;

rs748741;

rs754750;

rs7577213;

rs7648952;

rs7790530;

rs7822193;

rs7839244;

rs7852962;

rs7863519;

rs7922865;

rs849412;

rs906362;

rs919615;

rs942519;

rs979499;

rs9817233;

rs983513;

rs9841335;

rs9942691; and

rs9993666;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the subject'"'"'s likely response to administration of an antipsychotic.

17. A method of predicting degree of severity of a psychiatric endophenotype in a human subject, the method comprising:

obtaining a test haplotype for the subject by determining the genotype for at least one test marker listed in Table B, or at least one test markers that lies between the delimiting markers listed in Table A and that is in linkage disequilibrium (LD) with a marker in Table B,

wherein the test haplotype indicates the likely degree of severity of a psychiatric endophenotype in the subject.

18. The method of claim 17, wherein the psychiatric endophenotype is a quantitative trait that can be measured using one or more of PANSS Total composite score, PANSS Positive composite score, PANSS Negative composite score, and PANSS General Psychopathology composite score.

19. The method of claim 18, wherein one or more test markers are from potassium voltage-gated channel, delayed-rectifier, subfamily S, member 3 (KCNS3), Cas-Br-M (murine) ecotropic retroviral transforming sequence b (CBLB), janus kinase and microtubule interacting protein 1 (JAKMIP 1), or neurolysin (metallopeptidase M3 family) (NLN) genes and selected from among the group consisting of:

rs6713395;

rs4832524;

rs10804442;

rs13060223;

rs6807382;

rs7645021;

rs7649466;

rs1514326;

rs6446469;

rs252637; and

rs34980;

or is a test marker in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the likely degree of severity of a psychiatric endophenotype in the subject.

20. The method of claim 18, wherein the at least one test marker is selected from the group consisting of:

rs10033209;

rs10036380;

rs10045155;

rs10049102;

rs10180365;

rs1018313;

rs10229537;

rs10244871;

rs10255136;

rs10513278;

rs10804442;

rs10983070;

rs10983085;

rs10983437;

rs1107342;

rs11681604;

rs11682759;

rs1227919;

rs1232514;

rs12642020;

rs12673675;

rs13006199;

rs1301475;

rs13060223;

rs13074291;

rs13100218;

rs13290387;

rs1330811;

rs1352889;

rs1385405;

rs1393748;

rs1399650;

rs1405;

rs1406218;

rs1449629;

rs1471541;

rs1480617;

rs1480619;

rs1514326;

rs1515186;

rs152339;

rs1531111;

rs1888636;

rs214893;

rs2204859;

rs2215173;

rs2248213;

rs2248465;

rs2250861;

rs2252805;

rs2254485;

rs2271151;

rs2271385;

rs2274780;

rs2276322;

rs2279514;

rs2282084;

rs2300053;

rs2416;

rs252637;

rs2548788;

rs2581754;

rs2696398;

rs2701685;

rs2710672;

rs2727591;

rs2732509;

rs2900131;

rs2973488;

rs3103575;

rs3214046;

rs34980;

rs3731652;

rs3733212;

rs3733952;

rs3775433;

rs3796675;

rs3822290;

rs405485;

rs407200;

rs40848;

rs4502650;

rs4632953;

rs464494;

rs4668888;

rs4699415;

rs4699836;

rs4832524;

rs4853658;

rs582186;

rs582262;

rs6432705;

rs6446469;

rs6458705;

rs6532920;

rs6583623;

rs6713395;

rs6730450;

rs6734760;

rs6759206;

rs6788511;

rs6795556;

rs6807382;

rs6859984;

rs6934867;

rs726471;

rs729712;

rs7341041;

rs7355529;

rs7462663;

rs748741;

rs7577213;

rs7593724;

rs7645021;

rs7646842;

rs7649466;

rs7657032;

rs940261;

rs940262;

rs979375;

rs979499;

rs9823803;

rs983513;

rs9836453;

rs984610;

rs994011;

rs9993666;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the likely degree of severity of a psychiatric endophenotype.

21. The method of claim 17, wherein the psychiatric endophenotype comprises one or more of:

a Positive Symptom selected from the group consisting of P1-delusions, P2-conceptual disorganization, P3 -hallucinatory behavior, P4-exitement, P5-grandiosity, P6-suspiciousness, P7-hostility;

a Negative Symptom selected from the group consisting of N1-blunted affect, N2-emotional withdrawal, N3-poor rapport, N4-passive/appathetic social withdrawal, N5-difficultiy in abstract thinking, N6-lack of spontaneity and flow of conversation, N7-steryotyped thinking;

or a general psychopathology symptom selected from the group consisting of G1-somatic concern, G2-anxiety, G3-guilt feelings, G4-tension, G5-mannerisms and posturing, G6-depression, G7-motor retardation, G8-uncooperativeness, G9-unusual thought content, G10-disorentation, G11-poor attention, G12-lack of judgment and insight, G13 disturbance of volition, G14-poor impulse control, G15-preoccupation, and G16-active social avoidance.

22. The method of claim 21, wherein the at least one test marker is from a gene selected from the group consisting of ATPase, H+ transporting, lysosomal V1 subunit C2 (ATP6V1C2), glutamate decarboxylase-like I (GADL 1), catenin (cadherin-associated protein), delta 2 (neural plakophilin-related arm-repeat protein) (CTNND2), diacylglycerol kinase, beta 90 kDa (DGKB), and calneuron 1(CALN1), and further is selected from the group consisting of:

rs4669613;

rs9850620;

rs711684;

rs1393748;

rs9823803;

rs10036380;

rs1697902;

rs249264;

rs249264;

rs2530910;

rs2530910;

rs258630;

rs2727591;

rs2727591;

rs2973488;

rs10229537;

rs10255136;

rs10255136;

rs10255136;

rs1232514;

rs1232515;

rs1232515;

rs1232515;

rs573092;

rs573092;

rs573092; and

rs6461117;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the likely severity of a psychiatric endophenotype.

23. The method of claim 22, wherein the at least one test marker is selected from the group consisting of:

rs10033209;

rs10036380;

rs10036913;

rs10077289;

rs10180365;

rs10189040;

rs10229537;

rs10255136;

rs1047064;

rs10513278;

rs10762075;

rs10804442;

rs10817025;

rs10817865;

rs10900954;

rs10983070;

rs10983085;

rs10983437;

rs10995555;

rs11682759;

rs11948805;

rs12265366;

rs1232514;

rs1232515;

rs12536620;

rs12642020;

rs12667819;

rs12670550;

rs12673675;

rs12692275;

rs13006199;

rs1301475;

rs13029846;

rs13060223;

rs13074291;

rs13100218;

rs13130069;

rs13290387;

rs13499;

rs1393748;

rs1405;

rs1406218;

rs1449629;

rs1456359;

rs1471541;

rs1480617;

rs1480619;

rs1514326;

rs1525088;

rs1526083;

rs1608890;

rs1670146;

rs1697902;

rs17076802;

rs17108378;

rs17515800;

rs1881597;

rs1888636;

rs1905717;

rs1911490;

rs2105702;

rs2142325;

rs2215173;

rs2248213;

rs2248465;

rs2250861;

rs2254485;

rs2271385;

rs2276322;

rs2289914;

rs2293353;

rs2300053;

rs2390258;

rs249264;

rs252637;

rs2530910;

rs2548788;

rs258630;

rs2600072;

rs2701685;

rs2727591;

rs2850359;

rs2924307;

rs2973488;

rs3214046;

rs34980;

rs353119;

rs3731652;

rs3733212;

rs3733952;

rs3734960;

rs3736394;

rs3775433;

rs381318;

rs3817522;

rs404287;

rs405485;

rs407200;

rs4256135;

rs428459;

rs4452539;

rs4502650;

rs4668888;

rs4668909;

rs4669613;

rs4699415;

rs4699836;

rs4853658;

rs4858798;

rs4858828;

rs4858831;

rs4960635;

rs573092;

rs582186;

rs582262;

rs6431648;

rs6458705;

rs6461117;

rs6532920;

rs6555913;

rs6711120;

rs6730450;

rs6759206;

rs6807382;

rs6812406;

rs6934867;

rs6943314;

rs6958498;

rs7047593;

rs7092601;

rs711684;

rs726471;

rs729712;

rs7577213;

rs7593724;

rs7645021;

rs7646842;

rs7649466;

rs7722711;

rs7903280;

rs849412;

rs881572;

rs915281;

rs9651326;

rs9823803;

rs983513;

rs9836453;

rs984576;

rs9850620; and

rs994011;

or is a test marker that is in linkage disequilibrium with one of these markers, wherein the test haplotype indicates the likely degree of severity of a psychiatric endophenotype.

37. An array comprising a substrate having a plurality of addressable areas, wherein one or more of the addressable areas comprises a probe that can be used to detect a polymorphism that is listed in Table B or is in linkage disequilibrium with a marker listed in Table B.

38. A method of selecting a subject for administration of a treatment for schizophrenia (SZ), schizotypal personality disorder (SPD), or schizoaffective disorder (SD), the method comprising:

obtaining a haplotype for the subject, wherein the haplotype comprises at least one marker that is listed in Table B or is in linkage disequilibrium with a marker listed in Table B;

determining whether the haplotype is associated with an improved response profile for a clinical treatment; and

selecting the subject if the haplotype indicates that the subject is more likely to have an improved response profile to the clinical treatment in question.

39. A method of selecting a treatment for a subject, the method comprising:

obtaining a haplotype for the subject, wherein the haplotype comprises at least one marker that is listed in Table B or is in linkage disequilibrium with a marker listed in Table B;

determining whether the haplotype is associated with an improved response profile for a clinical treatment; and

selecting the treatment if the haplotype indicates that the subject is more likely to have an improved response profile to the clinical treatment in question.

40. A method of identifying haplotypes associated with altered outcome to a treatment for schizophrenia (SZ), schizotypal personality disorder (SPD), or schizoaffective disorder (SD), the method comprising obtaining a haplotype for a subject, wherein the haplotype comprises at least one marker that is listed in Table B or is in linkage disequilibrium with a marker listed in Table B;

obtaining data regarding response to a treatment in the subject; and

correlating the haplotype with a response to the clinical treatment.

41. The method of claim 40, wherein the data regarding response to a treatment comprises at least one parameter selected from the group consisting of efficacy, side-effect profile, treatment maintenance and discontinuation rates, return to work status, hospitalizations, suicidality, total healthcare cost, social functioning scales, response to non-pharmacological treatments, and dose response curves.

42. The method of claim 41, wherein the side-effect profile includes one or more of weight gain, metabolic dysfunction, lipid dysfunction, movement disorders, and extrapyramidal symptoms.

43. The method of claim 40, wherein the information regarding outcome of the treatment is from a clinical trial.

44. A method of providing information regarding one or more of the following:

a subject'"'"'s risk of developing schizophrenia (SZ), clinical response to antipsychotic medications, or severity of psychopathology endophenotypes, the method comprising;

obtaining a sample from the subject at a first site, transferring the sample to a second site for analysis, wherein the analysis provides data regarding the identity, presence or absence of at least one test marker that is listed in Table B or is in linkage disequilibrium with a marker listed in Table B;

analyzing the data for potential impact on one or more of the following;

a subject'"'"'s risk of developing schizophrenia (SZ);

clinical response to antipsychotic medications; and

presence or severity of psychiatric endophenotypes; and

transferring the results of the analysis to one or more of the following;

a health care provider;

the subject;

a healthcare payer;

or a clinical trial sponsor.

45. The method of claim 44, wherein the data is transferred to a healthcare payer and used to decide whether to reimburse a health care provider or subject for medical expenses, including drug costs.