Ncomms-18-33880B

ORE Open Research Exeter

TITLE Genome-wide association study identiﬁes genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates.

AUTHORS Dashti, HS; Jones, SE; Wood, AR; et al.

JOURNAL Nature Communications

DEPOSITED IN ORE 15 March 2019

This version available at

http://hdl.handle.net/10871/36477

Open Research Exeter makes this work available in accordance with publisher policies.

A NOTE ON VERSIONS

The version presented here may diﬀer from the published version. If citing, you are advised to consult the published version for pagination, volume/issue and date of publication NCOMMS-18-33880B

Dashti et al. a. Sleep Duration Heritability = 9.8 (0.1)% ) P ( 10 log -

Chromosome 1 2 3 4 5 6 7 10 11 14 17 19 C1orf94 PAX8 PCCB BANK1 PAM SCAND3 FOXP2 LOC100131719 HSD17B12 LOC100128215 LOC644157 PIN1 GJB5 LOC100130100 PPP2R3A LCORL PPIP5K2 LOC646160 MAD1L1 GPR26 METT5D1 PRKD1 LOC644172 OLFM2 PDE4B VRK2 STAG1 LOC645174 GIN1 FAM83B CHCHD3 MLLT10 OR2BH1P NOVA1 PER1 DAB1 GALNT3 MSL2 PRKG2 C5ORF30 MEA1 DNAJC1 C11orf63 ADCK1 PFAS DPYD SCN1A BBX, CCSER1 SLC6A3 PPP2R5D 8 SKIDA1 DRD2 FRDAP SMAD5-AS5 20 TTC21B LOC285205 LOC100132531 SMAD5-AS2 PPP1R3B EGR2 PTPRJ RTN1 VAMP2 YWHAB PABPCP2 LOC100128160 LOC285577 SRF PABPC1L LOC100129150 ADO OR4X2 12 FNTB AURKB LOC100133235 FOXP1 FGFR4 CUL7 FGF8 OR4B1 GPX2 ARHGEF15 SLC8A1 IL20RB V27 SLC34A1 DNPH1 KSR2 9 NFKB2 OR4S1 MVK MAX RANGRF MBOAT2 NPM1P17 RGS14 CUL9 ZCCHC7 PITX3 OR4X1 CHURC1 BORCS6 MAP2 ERC2 LMAN2 MRPL2 KCTD10 MRPL41 PSD TRPC6 UBE3B RAB15 CTC1, SPOPL PRELID1 TTBK1 EHMT1 FBXW4 ARCN1 TMEM107 GPD2 NSD1 RRP36 MYO1H ARRDC1-AS1 GBF1 KMT2A MMAB 15 KRBA2 NR4A2 MXD3 KLC4 ARRDC1 LDB1 IFT46 SEMA6D SLC25A35 CDC25C KLHDC3 DPH7 BTRC TMEM25 CA10 EGR1 LOC100129847 ZMYND19 NOLC1 LOC729790 LOC339209 ETF1 LOC100128159 NPM3 LOC646195 GFRA3 PNRC1 MGEA5 BUD13 16 18 HSPA9 KIFC1, PHF1 PPRC1 POLL GRM5 FTO TCF4 NME5 SYNGAP1 KCNIP2 CUEDC2 CA10 CDC23 GNAO1 CUTA FBXL15 LOC339209 RBFOX1 KIF20A C10ORF76 MYRF BRD8 HPS6 V27 TMEM258 PRKCB FAM53C C10orf95 FEN1 REEP2 ELOVL3 FADS1 KDM3B FADS3 SMAD5 RAB3IL1 SMAD5-AS1 FADS2 b. TRPC7

2 3 5 PAX8 AMT, APEH, RHOA, DAG1, SMAD5 11 GNAI2, GNAT1, GPX1, HYAL1, Short Sleep METT5D1 Heritability = 7.9 (0.1)% LOC100130100 SMAD5-AS1 OR2BH1P MST1, MST1R, SEMA3F, TRPC7 LOC647016 TCTA, UBA7 USP4, IFRD2, NDUFS3 LOC100131953 POLS 1 SEMA3B, HYAL3 HYAL2, BSN, LOC100130063 7 PSMC3 LMOD1 CACNA2D2, IP6K1, RBM6, FOXP2 PTPRJ PAM MAD1L1 RAPSN IPO9 RBM5, TRAIP, NPRL2, PPIP5K2 6 NAV1 SLC38A3, CYB561D2, GIN1 ZSCAN12 CELF1 16 18 ZSCAN31 NUP160 TCF4 SHISA4 TMEM115, RASSF1, TUSC2, c5orf30 GNAO1 22 DPYD NAT6, GMPPB, ZMYND10, ZKSCAN3 FNBP4 4 8 15 MGAT3 ) PDE4B RNF123, CAMKV, NICN1, SLC39A8 HCRTR2 MTCH2 USP49 PCMTD1 KBTBD4 SEMA6D SYNGR P C1orf94 GJB5 MON1A, LSMEM2, AMIGO3 PRKG2

( PXDNL TAB1 FAM212A, ACTBP13 LAMA2 AGBL2 17

10 C1QTNF4 SHISA6 log -

4 ) P (

10 6 log - 8 1 11 17 CAMTA1 MPZL2 KIAA1267 5 JAML 16 LOC644246 RAB3C FTO PDE4D MPZL3 10 C11orf63 GUCY2E

2 PAX8 12 LOC100130100 Long Sleep Heritability = 4.7 (0.1)% a. GO_cc:go_neuron_projectionGO_cc:go_neur on_projection GO_cc:go_somatodendritic_compartmentGO_cc:go_somatode ndritic_compartme nt

GO_bp:go_a denylate_cyclase_GO_bp:go_adenylate_cyclase_activating activating_ g_protein_coupled_ rece ptor_ signa ling__ pathwaygpcr_signaling_pathway GO_bp:go_response_to_auditory_stimulusGO_bp:go_r esponse_to_aud ito ry_stimulus

Curated_gCurated_gene_sets:ivanova_hematopoiesis ene_sets:ivanova_hemato poiesis_ea rly_progenitor _early_progenitor GO_bp:go_synapticGO_bp:go_synapt ic_signalingsignaling

GO_bp:go_subpallium_developmentGO_bp:go_sub pallium_ development MAGMA

GO_mf:go_dopamine_bindingGO_mf:go_d opamine_binding

GO_bp:go_mechanosensory_behaviorGO_bp:go_m echanosensory_beha vior

GO_bp:go_striatum_developmentGO_bp:go_str iatum_development TH

0 2 4 6 8 HTT GLI3 DLX1 DLX2 ETV1 BBS2 BBS4 FGF8 GSX2 DRD1 DRD2 DRD3 DRD4 DRD5 RARB MKKS OGDH INHBA ASCL1 STRA6 FOXP2 GPR21 GPR52 ADRB2 STRBP Enrichment -log (P) NRXN1 NRXN2 10 BCL11B SLC1A3 SLC6A3 SHANK3 SLITRK5 SLITRK6 ALDH1A3 CNTNAP2 b. c. SECISBP2

) 7 ) P P ( 6 ( 10 10 5 log log - - 4 3 2

Enrichment Enrichment 1 Enrichment Enrichment 0

KEGG_GAP_JUNCTION REACTOME_HEMOSTASIS

REACTOME_MEIOTIC_SYNAPSIS KEGG_LONG_TERM_DEPRESSIONREACTOME_NEURONAL_SYSTEM REACTOME_SIGNALING_BY_FGFR KEGG_MAPK_SIGNALING_PATHWAY

REACTOME_PLC_BETA_MEDIATED_EVENTS REACTOME_SIGNALING_BY_FGFR_I N_DISEASE

REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES PASCAL MAGMA Sleep Duration * * * * * *

Short Sleep * * * * * * *

Long Sleep * * * * * * * * c. a. SNP effect on sleep duration, minutes SNP effect on schizophrenia, log odds SNP effect on Schizophrenia || id:22 − 0.00 0.05 0.10 0.05 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● SNP effect on schizophrenia, log odds log schizophrenia, on effect SNP ● ● ● ● ● ● ● ● SNP effect on sleep duration, minutes duration, sleep on effect SNP ● ● ● ● ● ● ● ● ● ● ● ● SNP effect onmrbase_sleepduration_schizophrenia.csv ● ● ● ● ● ● 1.0 ● ● ● ● ● ● ● ● MR Test ● ● ● ● ● MR Egger Inverse variance weighted ● ● ● ● ● ● 1.5 ● ● Weighted median ● 2.0 ● ● ● 2.5 d. b. MR effect of schizophrenia on sleep sleep on schizophrenia of effect MR MR effect of sleep duration on on duration sleep of effect MR schizophrenia, log odds log schizophrenia, duration, minutes duration,