DNA sequence-level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders
Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and fam...
Uložené v:
| Vydané v: | Molecular psychiatry Ročník 23; číslo 12; s. 2254 - 2265 |
|---|---|
| Hlavní autori: | , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
England
Nature Publishing Group
01.12.2018
|
| Predmet: | |
| ISSN: | 1359-4184, 1476-5578, 1476-5578 |
| On-line prístup: | Získať plný text |
| Tagy: |
Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
|
| Abstract | Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes. |
|---|---|
| AbstractList | Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes.Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes. Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes. |
| Author | McCarthy, Shane Deary, Ian J McIntosh, Andrew M Duff, Barbara Morris, Stewart W Arnau-Soler, Aleix Lawrie, Stephen M Porteous, David J Ryan, Niamh M Davies, Gail Kramer, Melissa Blackwood, Douglas H R Lihm, Jayon Thomson, Pippa A Evans, Kathryn L Ghiban, Elena McCombie, W Richard Hayward, Caroline |
| Author_xml | – sequence: 1 givenname: Niamh M surname: Ryan fullname: Ryan, Niamh M organization: Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK – sequence: 2 givenname: Jayon surname: Lihm fullname: Lihm, Jayon organization: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, USA – sequence: 3 givenname: Melissa surname: Kramer fullname: Kramer, Melissa organization: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, USA – sequence: 4 givenname: Shane surname: McCarthy fullname: McCarthy, Shane organization: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, USA – sequence: 5 givenname: Stewart W surname: Morris fullname: Morris, Stewart W organization: Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK – sequence: 6 givenname: Aleix surname: Arnau-Soler fullname: Arnau-Soler, Aleix organization: Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK – sequence: 7 givenname: Gail surname: Davies fullname: Davies, Gail organization: Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK – sequence: 8 givenname: Barbara surname: Duff fullname: Duff, Barbara organization: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK – sequence: 9 givenname: Elena surname: Ghiban fullname: Ghiban, Elena organization: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, USA – sequence: 10 givenname: Caroline orcidid: 0000-0002-9405-9550 surname: Hayward fullname: Hayward, Caroline organization: MRC Human Genetics Unit, MRC Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK – sequence: 11 givenname: Ian J surname: Deary fullname: Deary, Ian J organization: Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK – sequence: 12 givenname: Douglas H R orcidid: 0000-0002-4076-9346 surname: Blackwood fullname: Blackwood, Douglas H R organization: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK – sequence: 13 givenname: Stephen M orcidid: 0000-0002-2444-5675 surname: Lawrie fullname: Lawrie, Stephen M organization: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK – sequence: 14 givenname: Andrew M orcidid: 0000-0002-0198-4588 surname: McIntosh fullname: McIntosh, Andrew M organization: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK – sequence: 15 givenname: Kathryn L surname: Evans fullname: Evans, Kathryn L organization: Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK – sequence: 16 givenname: David J orcidid: 0000-0003-1249-6106 surname: Porteous fullname: Porteous, David J email: david.porteous@ed.ac.uk, david.porteous@ed.ac.uk, david.porteous@ed.ac.uk organization: Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. david.porteous@ed.ac.uk – sequence: 17 givenname: W Richard surname: McCombie fullname: McCombie, W Richard email: mccombie@cshl.edu organization: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, USA. mccombie@cshl.edu – sequence: 18 givenname: Pippa A orcidid: 0000-0002-4208-5271 surname: Thomson fullname: Thomson, Pippa A email: Pippa.Thomson@ed.ac.uk, Pippa.Thomson@ed.ac.uk organization: Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK. Pippa.Thomson@ed.ac.uk |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29880880$$D View this record in MEDLINE/PubMed |
| BookMark | eNpdkE1LxDAQhoOsuO7qD_AiAS9eoknTNOlxWT9h0YueS9pO3SxpWpNW6b83i-tFGJhnmIeBeRdo5joHCF0wesMoV7chZVxRQpkilCpJ0iN0ylKZESGkmkXmIicpU-kcLULYUbpfihM0T3KlaKxT5O5eVjjA5wiuAmLhCyzWTtspQMA-jtrivhvADWZPW3DdMPWmwm1Xm8aAD9g4rLHV_gNwo1tjJ_xthi3uw1RtjR58lGsTOl9H-QwdN9oGOD_0JXp_uH9bP5HN6-PzerUhVSrpQHgpkrqRQkvZMBWZJ6AqLaAEVgrKpWB5lXKdZFrWXAPNEsEAqiaPgSQ58CW6_r3b-y7-FoaiNaECa7WDbgxFQkWiaCY4j-rVP3XXjT5GEC0mslSJTLBoXR6ssWyhLnpvWu2n4i9J_gM91XhY |
| CitedBy_id | crossref_primary_10_3390_ijms25094930 crossref_primary_10_1016_j_biopsych_2020_06_011 crossref_primary_10_1111_gbb_12596 crossref_primary_10_1038_s41380_019_0429_x crossref_primary_10_3390_biom15050615 crossref_primary_10_1038_s41380_019_0505_2 crossref_primary_10_1038_s41398_018_0228_1 crossref_primary_10_1503_jpn_200083 crossref_primary_10_2147_CCID_S417805 crossref_primary_10_1177_23982128211009148 crossref_primary_10_1038_s41380_020_00947_5 crossref_primary_10_1038_s41398_021_01256_3 crossref_primary_10_1093_hmg_ddaa180 crossref_primary_10_1186_s12888_022_04304_4 crossref_primary_10_3390_ijms26104841 crossref_primary_10_1007_s11011_021_00692_w |
| ContentType | Journal Article |
| Copyright | 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
| Copyright_xml | – notice: 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
| DBID | CGR CUY CVF ECM EIF NPM 3V. 7TK 7X7 7XB 88E 88G 8AO 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. LK8 M0S M1P M2M M7P PHGZM PHGZT PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS PSYQQ Q9U 7X8 |
| DOI | 10.1038/s41380-018-0087-4 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed ProQuest Central (Corporate) Neurosciences Abstracts Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Psychology Database (Alumni) ProQuest Pharma Collection ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni Edition) ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Korea Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) ProQuest Biological Science Collection Health & Medical Collection (Alumni Edition) Medical Database Psychology Database Biological Science Database ProQuest Central Premium ProQuest One Academic (New) ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China ProQuest One Psychology ProQuest Central Basic MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest One Psychology ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Biological Science Collection ProQuest Central Basic ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) ProQuest Psychology Journals (Alumni) Biological Science Database ProQuest SciTech Collection Neurosciences Abstracts ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest Psychology Journals ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic ProQuest One Psychology MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1476-5578 |
| EndPage | 2265 |
| ExternalDocumentID | 29880880 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: National Centre for the Replacement, Refinement and Reduction of Animals in Research grantid: NC/C011202/1 – fundername: Wellcome Trust – fundername: Medical Research Council grantid: MC_UU_00007/10 – fundername: Medical Research Council grantid: MR/K026992/1 – fundername: Chief Scientist Office grantid: SCD/12 – fundername: Medical Research Council grantid: MR/J004367/1 – fundername: NCI NIH HHS grantid: P30 CA045508 – fundername: NIMH NIH HHS grantid: R01 MH102068 |
| GroupedDBID | --- -Q- 0R~ 123 29M 2WC 36B 39C 4.4 406 53G 70F 7X7 88E 8AO 8FI 8FJ 8R4 8R5 AACDK AANZL AASML AATNV AAYZH ABAKF ABAWZ ABBRH ABDBE ABDBF ABFSG ABIVO ABJNI ABLJU ABRTQ ABUWG ABZZP ACAOD ACGFS ACKTT ACPRK ACRQY ACSTC ACUHS ACZOJ ADBBV AEFQL AEJRE AEMSY AENEX AEVLU AEXYK AEZWR AFBBN AFDZB AFHIU AFKRA AFRAH AFSHS AGAYW AGHAI AGQEE AHMBA AHSBF AHWEU AIGIU AILAN AIXLP AJRNO ALFFA ALIPV ALMA_UNASSIGNED_HOLDINGS AMYLF ATHPR AXYYD AYFIA AZQEC B0M BAWUL BBNVY BENPR BHPHI BKKNO BPHCQ BVXVI CAG CCPQU CGR COF CS3 CUY CVF DIK DNIVK DPUIP DU5 DWQXO E3Z EAD EAP EBC EBD EBLON EBS ECM EE. EIF EIOEI EJD EMB EMK EMOBN EPL EPS ESX F5P FDQFY FEDTE FERAY FIGPU FIZPM FSGXE FYUFA GNUQQ HCIFZ HMCUK HVGLF HZ~ IAO IHR INH INR IPY ITC IWAJR JSO JZLTJ KQ8 M1P M2M M7P NPM NQJWS O9- OK1 OVD P2P PHGZM PHGZT PJZUB PPXIY PQGLB PQQKQ PROAC PSQYO PSYQQ Q2X RNS RNT RNTTT ROL SNX SNYQT SOHCF SOJ SRMVM SV3 SWTZT TAOOD TBHMF TDRGL TEORI TR2 TSG TUS UKHRP ~8M 3V. 7TK 7XB 8FE 8FH 8FK K9. LK8 PKEHL PQEST PQUKI PRINS Q9U 7X8 PUEGO |
| ID | FETCH-LOGICAL-c470t-3b52df75a77f1852d32e8ca5ebe1b5037519c43a26a7d3ae06251eecf913829e3 |
| IEDL.DBID | M7P |
| ISICitedReferencesCount | 13 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000453243900002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1359-4184 1476-5578 |
| IngestDate | Fri Sep 05 13:19:48 EDT 2025 Tue Oct 07 05:12:23 EDT 2025 Mon Jul 21 06:03:16 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 12 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c470t-3b52df75a77f1852d32e8ca5ebe1b5037519c43a26a7d3ae06251eecf913829e3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0000-0002-9405-9550 0000-0002-2444-5675 0000-0003-1249-6106 0000-0002-0198-4588 0000-0002-4076-9346 0000-0002-4208-5271 |
| OpenAccessLink | https://link.springer.com/article/10.1038/s41380-018-0087-4 |
| PMID | 29880880 |
| PQID | 2156485651 |
| PQPubID | 44096 |
| PageCount | 12 |
| ParticipantIDs | proquest_miscellaneous_2052806533 proquest_journals_2156485651 pubmed_primary_29880880 |
| PublicationCentury | 2000 |
| PublicationDate | 2018-12-01 |
| PublicationDateYYYYMMDD | 2018-12-01 |
| PublicationDate_xml | – month: 12 year: 2018 text: 2018-12-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England – name: New York |
| PublicationTitle | Molecular psychiatry |
| PublicationTitleAlternate | Mol Psychiatry |
| PublicationYear | 2018 |
| Publisher | Nature Publishing Group |
| Publisher_xml | – name: Nature Publishing Group |
| SSID | ssj0014765 |
| Score | 2.3725064 |
| Snippet | Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 2254 |
| SubjectTerms | Adult Alleles Behavior disorders Cognition Contactins - genetics Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics Disc1 protein Family - psychology Female Gene frequency Gene Frequency - genetics Genetic diversity Genetic Linkage - genetics Genetic Predisposition to Disease - genetics Genetic Testing Genome-Wide Association Study Genomes Genomics Genotype Heritability Humans Linkage analysis Lod Score Male Mental disorders Mental Disorders - genetics Mental Disorders - physiopathology Middle Aged Mood Disorders - genetics Multifactorial Inheritance Nerve Tissue Proteins - genetics Neuroimaging Nucleotide sequence Pedigree Phenotype Phenotypes Phenotypic variations Phosphodiesterase Receptor, Metabotropic Glutamate 5 - genetics Recombinant Fusion Proteins - genetics RNA, Long Noncoding RNA, Messenger - genetics Sequence Analysis, DNA - methods Translocation, Genetic |
| Title | DNA sequence-level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/29880880 https://www.proquest.com/docview/2156485651 https://www.proquest.com/docview/2052806533 |
| Volume | 23 |
| WOSCitedRecordID | wos000453243900002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3fa9swED76E_aydmu3Zm2DBn0VtSUrkp9Gtib0YTGhdCVvQZYUGkjtLHYL-e-nk53sqX0pGGFjyRjd-Xy6-_QdwFXOuVbeVaCslyuauNTRNFKaOnTOvf8gXCDSfvgts0xNJum4DbhVLaxyYxODobalwRj5NUNWE-UHxz-WfylWjcLsaltCYxf2kSWBB-jeeJtFSGQoJRlzgdlOlWyymlxdV954K4RkKYqsbDR53cMMf5rh0Xvf8Rg-tj4m6TdK8Ql2XPEZDpuqk-sTKG6yPtlAqOkCUUNEB24SVxFkdPJjl2WNMCI8e3RFWa-Xc0OeSjufYelsMi-IJgsEkZMmQkIwnku20Gnf2ba0ntUp_BkO7n_d0rbsAjWJjGrKc8HsTAot5Qy3VlvOnDJaeHHHucCauXFqEq5ZT0vLtYv8Eip2zsxS5DNMHf8Ce0VZuDMgKremZ00iwhbcHtMq8QsaEeXaCi-VvAMXm4mctt9ONf0_ix34vr3ttR5TGbpw5bPvE4mQEua8A18bYU2XDT3HlKXeJvnj29sPP4cPDMUfoCkXsFevnt0lHJiXel6turArJzK0qgv7PwfZ-M5fjdioG1TMt9l49A87P9Y- |
| linkProvider | ProQuest |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Nb9QwEB2VFgSXlo8CCy0YCY5WE39snAOqKtqqVXdXHArqLTi2V6xUkqVJQfun-hs742yWE9x6QMohUmxLiSfjGc_zewDvSymtwVCBi2FpuAp54HliLA8UnGP8oEMk0v46yiYTc3GRf16Dm_4sDMEqe58YHbWvHe2R7wliNTHYOd2f_-SkGkXV1V5CozOLs7D4jSlb8_H0EOf3gxDHR-efTvhSVYA7lSUtl6UWfpppm2VTOjnspQjGWY1vk5aaJGHT3ClpxdBmXtqQYIaQhuCmOdH15UHiuPdgQ2EmRFIRYzFeVS1UFqUrU6mpumpUX0WVZq_BxcIQBMxwYoHj6u8RbVzZjrf-t2_yGDaXMTQ76Iz-CayF6ik86FQ1F8-gOpwcsB4izi8JFcVs5F4JDSPGKuw7r1uCSdHd91DV7WI-c-xH7WdTkgZns4pZdkkgedbtADHar2YraDg29kva0mYbvtzJyz6H9aquwktgpvRu6J3S8YjxUFijMGHTSWm9RisoB7DTT1yx9A1N8WfWBvBu9Rj_airV2CrU19gm0bHkLeUAXnTGUcw7-pFC5Ohz8Xr178HfwsOT8_GoGJ1Ozl7DI0GmF2E4O7DeXl2HXbjvfrWz5upNNGIG3-7aQm4BYz4taA |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Nb9QwEB2VFhAXSvlcKNRIcLQ2seONc6hQxXZF1Wq1B0C9Bcd2xEolWZoUtH-NX9cZJ1lO9NYDUg6RYlty_Dwee57fALwrpDQaXQUuJoXmic88zyJtuCfnHP0H5YOQ9tezdD7X5-fZYgv-DHdhiFY52MRgqF1t6Yx8LEjVRGPleFz2tIjFdPZh9ZNTBimKtA7pNDqInPr1b9y-NYcnUxzr90LMjj9__MT7DAPcJmnUclko4cpUmTQt6Raxk8JraxT2LC4UpYeNM5tIIyYmddL4CHcLsfe2zEi6L_MS270DOymJlgfa4GITwUjSkMYylooirToZIqpSjxtcODTRwTQnRTie_Nu7DavcbPd__j-P4GHvW7OjbjLswZavHsO9Ltvm-glU0_kRG6jj_ILYUswETRbfMFKywrqruiX6FL1991XdrldLy37UbllSynC2rJhhF0SeZ93JEKNzbLahjGNh18uZNk_hy6109hlsV3XlXwDThbMTZxMVrh5PhNEJbuRUVBinEBHFCPaHQcx7m9Hkf0dwBG83n3G2UwjHVL6-wjKRCqFwKUfwvANKvupkSXKRoS3G5-XNjR_AfQRGfnYyP30FDwShMLBz9mG7vbzyr-Gu_dUum8s3Ac8Mvt02QK4BspI2OQ |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=DNA+sequence-level+analyses+reveal+potential+phenotypic+modifiers+in+a+large+family+with+psychiatric+disorders&rft.jtitle=Molecular+psychiatry&rft.au=Ryan%2C+Niamh+M&rft.au=Lihm%2C+Jayon&rft.au=Kramer%2C+Melissa&rft.au=McCarthy%2C+Shane&rft.date=2018-12-01&rft.pub=Nature+Publishing+Group&rft.issn=1359-4184&rft.eissn=1476-5578&rft.volume=23&rft.issue=12&rft.spage=2254&rft.epage=2265&rft_id=info:doi/10.1038%2Fs41380-018-0087-4&rft.externalDBID=HAS_PDF_LINK |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1359-4184&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1359-4184&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1359-4184&client=summon |