Stefansson K

References (6)

Title : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity - Turcot_2018_Nat.Genet_50_26
Author(s) : Turcot V , Lu Y , Highland HM , Schurmann C , Justice AE , Fine RS , Bradfield JP , Esko T , Giri A , Graff M , Guo X , Hendricks AE , Karaderi T , Lempradl A , Locke AE , Mahajan A , Marouli E , Sivapalaratnam S , Young KL , Alfred T , Feitosa MF , Masca NGD , Manning AK , Medina-Gomez C , Mudgal P , Ng MCY , Reiner AP , Vedantam S , Willems SM , Winkler TW , Abecasis G , Aben KK , Alam DS , Alharthi SE , Allison M , Amouyel P , Asselbergs FW , Auer PL , Balkau B , Bang LE , Barroso I , Bastarache L , Benn M , Bergmann S , Bielak LF , Bluher M , Boehnke M , Boeing H , Boerwinkle E , Boger CA , Bork-Jensen J , Bots ML , Bottinger EP , Bowden DW , Brandslund I , Breen G , Brilliant MH , Broer L , Brumat M , Burt AA , Butterworth AS , Campbell PT , Cappellani S , Carey DJ , Catamo E , Caulfield MJ , Chambers JC , Chasman DI , Chen YI , Chowdhury R , Christensen C , Chu AY , Cocca M , Collins FS , Cook JP , Corley J , Corominas Galbany J , Cox AJ , Crosslin DS , Cuellar-Partida G , D'Eustacchio A , Danesh J , Davies G , Bakker PIW , Groot MCH , Mutsert R , Deary IJ , Dedoussis G , Demerath EW , Heijer M , Hollander AI , Ruijter HM , Dennis JG , Denny JC , Angelantonio E , Drenos F , Du M , Dube MP , Dunning AM , Easton DF , Edwards TL , Ellinghaus D , Ellinor PT , Elliott P , Evangelou E , Farmaki AE , Farooqi IS , Faul JD , Fauser S , Feng S , Ferrannini E , Ferrieres J , Florez JC , Ford I , Fornage M , Franco OH , Franke A , Franks PW , Friedrich N , Frikke-Schmidt R , Galesloot TE , Gan W , Gandin I , Gasparini P , Gibson J , Giedraitis V , Gjesing AP , Gordon-Larsen P , Gorski M , Grabe HJ , Grant SFA , Grarup N , Griffiths HL , Grove ML , Gudnason V , Gustafsson S , Haessler J , Hakonarson H , Hammerschlag AR , Hansen T , Harris KM , Harris TB , Hattersley AT , Have CT , Hayward C , He L , Heard-Costa NL , Heath AC , Heid IM , Helgeland O , Hernesniemi J , Hewitt AW , Holmen OL , Hovingh GK , Howson JMM , Hu Y , Huang PL , Huffman JE , Ikram MA , Ingelsson E , Jackson AU , Jansson JH , Jarvik GP , Jensen GB , Jia Y , Johansson S , Jorgensen ME , Jorgensen T , Jukema JW , Kahali B , Kahn RS , Kahonen M , Kamstrup PR , Kanoni S , Kaprio J , Karaleftheri M , Kardia SLR , Karpe F , Kathiresan S , Kee F , Kiemeney LA , Kim E , Kitajima H , Komulainen P , Kooner JS , Kooperberg C , Korhonen T , Kovacs P , Kuivaniemi H , Kutalik Z , Kuulasmaa K , Kuusisto J , Laakso M , Lakka TA , Lamparter D , Lange EM , Lange LA , Langenberg C , Larson EB , Lee NR , Lehtimaki T , Lewis CE , Li H , Li J , Li-Gao R , Lin H , Lin KH , Lin LA , Lin X , Lind L , Lindstrom J , Linneberg A , Liu CT , Liu DJ , Liu Y , Lo KS , Lophatananon A , Lotery AJ , Loukola A , Luan J , Lubitz SA , Lyytikainen LP , Mannisto S , Marenne G , Mazul AL , McCarthy MI , McKean-Cowdin R , Medland SE , Meidtner K , Milani L , Mistry V , Mitchell P , Mohlke KL , Moilanen L , Moitry M , Montgomery GW , Mook-Kanamori DO , Moore C , Mori TA , Morris AD , Morris AP , Muller-Nurasyid M , Munroe PB , Nalls MA , Narisu N , Nelson CP , Neville M , Nielsen SF , Nikus K , Njolstad PR , Nordestgaard BG , Nyholt DR , O'Connel JR , O'Donoghue ML , Olde Loohuis LM , Ophoff RA , Owen KR , Packard CJ , Padmanabhan S , Palmer CNA , Palmer ND , Pasterkamp G , Patel AP , Pattie A , Pedersen O , Peissig PL , Peloso GM , Pennell CE , Perola M , Perry JA , Perry JRB , Pers TH , Person TN , Peters A , Petersen ERB , Peyser PA , Pirie A , Polasek O , Polderman TJ , Puolijoki H , Raitakari OT , Rasheed A , Rauramaa R , Reilly DF , Renstrom F , Rheinberger M , Ridker PM , Rioux JD , Rivas MA , Roberts DJ , Robertson NR , Robino A , Rolandsson O , Rudan I , Ruth KS , Saleheen D , Salomaa V , Samani NJ , Sapkota Y , Sattar N , Schoen RE , Schreiner PJ , Schulze MB , Scott RA , Segura-Lepe MP , Shah SH , Sheu WH , Sim X , Slater AJ , Small KS , Smith AV , Southam L , Spector TD , Speliotes EK , Starr JM , Stefansson K , Steinthorsdottir V , Stirrups KE , Strauch K , Stringham HM , Stumvoll M , Sun L , Surendran P , Swift AJ , Tada H , Tansey KE , Tardif JC , Taylor KD , Teumer A , Thompson DJ , Thorleifsson G , Thorsteinsdottir U , Thuesen BH , Tonjes A , Tromp G , Trompet S , Tsafantakis E , Tuomilehto J , Tybjaerg-Hansen A , Tyrer JP , Uher R , Uitterlinden AG , Uusitupa M , Laan SW , Duijn CM , Leeuwen N , van Setten J , Vanhala M , Varbo A , Varga TV , Varma R , Velez Edwards DR , Vermeulen SH , Veronesi G , Vestergaard H , Vitart V , Vogt TF , Volker U , Vuckovic D , Wagenknecht LE , Walker M , Wallentin L , Wang F , Wang CA , Wang S , Wang Y , Ware EB , Wareham NJ , Warren HR , Waterworth DM , Wessel J , White HD , Willer CJ , Wilson JG , Witte DR , Wood AR , Wu Y , Yaghootkar H , Yao J , Yao P , Yerges-Armstrong LM , Young R , Zeggini E , Zhan X , Zhang W , Zhao JH , Zhao W , Zhou W , Zondervan KT , Rotter JI , Pospisilik JA , Rivadeneira F , Borecki IB , Deloukas P , Frayling TM , Lettre G , North KE , Lindgren CM , Hirschhorn JN , Loos RJF
Ref : Nat Genet , 50 :26 , 2018
Abstract : Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
ESTHER : Turcot_2018_Nat.Genet_50_26
PubMedSearch : Turcot_2018_Nat.Genet_50_26
PubMedID: 29273807

Title : Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis - Sigurdsson_2017_Nat.Commun_8_15789
Author(s) : Sigurdsson S , Alexandersson KF , Sulem P , Feenstra B , Gudmundsdottir S , Halldorsson GH , Olafsson S , Sigurdsson A , Rafnar T , Thorgeirsson T , Sorensen E , Nordholm-Carstensen A , Burcharth J , Andersen J , Jorgensen HS , Possfelt-Moller E , Ullum H , Thorleifsson G , Masson G , Thorsteinsdottir U , Melbye M , Gudbjartsson DF , Stefansson T , Jonsdottir I , Stefansson K
Ref : Nat Commun , 8 :15789 , 2017
Abstract : Diverticular disease is characterized by pouches (that is, diverticulae) due to weakness in the bowel wall, which can become infected and inflamed causing diverticulitis, with potentially severe complications. Here, we test 32.4 million sequence variants identified through whole-genome sequencing (WGS) of 15,220 Icelanders for association with diverticular disease (5,426 cases) and its more severe form diverticulitis (2,764 cases). Subsequently, 16 sequence variants are followed up in a diverticular disease sample from Denmark (5,970 cases, 3,020 controls). In the combined Icelandic and Danish data sets we observe significant association of intronic variants in ARHGAP15 (Rho GTPase-activating protein 15; rs4662344-T: P=1.9 x 10-18, odds ratio (OR)=1.23) and COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T: P=1.5 x 10-10, OR=0.87) with diverticular disease and in FAM155A (family with sequence similarity 155A; rs67153654-A: P=3.0 x 10-11, OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study.
ESTHER : Sigurdsson_2017_Nat.Commun_8_15789
PubMedSearch : Sigurdsson_2017_Nat.Commun_8_15789
PubMedID: 28585551

Title : Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence - Hancock_2015_Transl.Psychiatry_5_e651
Author(s) : Hancock DB , Reginsson GW , Gaddis NC , Chen X , Saccone NL , Lutz SM , Qaiser B , Sherva R , Steinberg S , Zink F , Stacey SN , Glasheen C , Chen J , Gu F , Frederiksen BN , Loukola A , Gudbjartsson DF , Bruske I , Landi MT , Bickeboller H , Madden P , Farrer L , Kaprio J , Kranzler HR , Gelernter J , Baker TB , Kraft P , Amos CI , Caporaso NE , Hokanson JE , Bierut LJ , Thorgeirsson TE , Johnson EO , Stefansson K
Ref : Transl Psychiatry , 5 :e651 , 2015
Abstract : We conducted a 1000 Genomes-imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerstrom Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P=8.0 x 10(-9) across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12 and 95% confidence interval=1.08-1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P=7.3 x 10(-4)). Importantly, rs2273500-C was associated with increased lung cancer risk (N=28 998, odds ratio=1.06 and 95% confidence interval=1.00-1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single 'cigarettes per day' item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences.
ESTHER : Hancock_2015_Transl.Psychiatry_5_e651
PubMedSearch : Hancock_2015_Transl.Psychiatry_5_e651
PubMedID: 26440539

Title : Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers - Hartz_2012_Arch.Gen.Psychiatry_69_854
Author(s) : Hartz SM , Short SE , Saccone NL , Culverhouse R , Chen L , Schwantes-An TH , Coon H , Han Y , Stephens SH , Sun J , Chen X , Ducci F , Dueker N , Franceschini N , Frank J , Geller F , Gubjartsson D , Hansel NN , Jiang C , Keskitalo-Vuokko K , Liu Z , Lyytikainen LP , Michel M , Rawal R , Rosenberger A , Scheet P , Shaffer JR , Teumer A , Thompson JR , Vink JM , Vogelzangs N , Wenzlaff AS , Wheeler W , Xiao X , Yang BZ , Aggen SH , Balmforth AJ , Baumeister SE , Beaty T , Bennett S , Bergen AW , Boyd HA , Broms U , Campbell H , Chatterjee N , Chen J , Cheng YC , Cichon S , Couper D , Cucca F , Dick DM , Foroud T , Furberg H , Giegling I , Gu F , Hall AS , Hallfors J , Han S , Hartmann AM , Hayward C , Heikkila K , Hewitt JK , Hottenga JJ , Jensen MK , Jousilahti P , Kaakinen M , Kittner SJ , Konte B , Korhonen T , Landi MT , Laatikainen T , Leppert M , Levy SM , Mathias RA , McNeil DW , Medland SE , Montgomery GW , Muley T , Murray T , Nauck M , North K , Pergadia M , Polasek O , Ramos EM , Ripatti S , Risch A , Ruczinski I , Rudan I , Salomaa V , Schlessinger D , Styrkarsdottir U , Terracciano A , Uda M , Willemsen G , Wu X , Abecasis G , Barnes K , Bickeboller H , Boerwinkle E , Boomsma DI , Caporaso N , Duan J , Edenberg HJ , Francks C , Gejman PV , Gelernter J , Grabe HJ , Hops H , Jarvelin MR , Viikari J , Kahonen M , Kendler KS , Lehtimaki T , Levinson DF , Marazita ML , Marchini J , Melbye M , Mitchell BD , Murray JC , Nothen MM , Penninx BW , Raitakari O , Rietschel M , Rujescu D , Samani NJ , Sanders AR , Schwartz AG , Shete S , Shi J , Spitz M , Stefansson K , Swan GE , Thorgeirsson T , Volzke H , Wei Q , Wichmann HE , Amos CI , Breslau N , Cannon DS , Ehringer M , Grucza R , Hatsukami D , Heath A , Johnson EO , Kaprio J , Madden P , Martin NG , Stevens VL , Stitzel JA , Weiss RB , Kraft P , Bierut LJ
Ref : Arch Gen Psychiatry , 69 :854 , 2012
Abstract : CONTEXT: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. OBJECTIVE: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. DATA SOURCES: Primary data. STUDY SELECTION: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DATA EXTRACTION: Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD </=10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset </=16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. DATA SYNTHESIS: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). CONCLUSION: These results highlight an increased genetic vulnerability to smoking in early-onset smokers.
ESTHER : Hartz_2012_Arch.Gen.Psychiatry_69_854
PubMedSearch : Hartz_2012_Arch.Gen.Psychiatry_69_854
PubMedID: 22868939

Title : Common variants conferring risk of schizophrenia - Stefansson_2009_Nature_460_744
Author(s) : Stefansson H , Ophoff RA , Steinberg S , Andreassen OA , Cichon S , Rujescu D , Werge T , Pietilainen OP , Mors O , Mortensen PB , Sigurdsson E , Gustafsson O , Nyegaard M , Tuulio-Henriksson A , Ingason A , Hansen T , Suvisaari J , Lonnqvist J , Paunio T , Borglum AD , Hartmann A , Fink-Jensen A , Nordentoft M , Hougaard D , Norgaard-Pedersen B , Bottcher Y , Olesen J , Breuer R , Moller HJ , Giegling I , Rasmussen HB , Timm S , Mattheisen M , Bitter I , Rethelyi JM , Magnusdottir BB , Sigmundsson T , Olason P , Masson G , Gulcher JR , Haraldsson M , Fossdal R , Thorgeirsson TE , Thorsteinsdottir U , Ruggeri M , Tosato S , Franke B , Strengman E , Kiemeney LA , Melle I , Djurovic S , Abramova L , Kaleda V , Sanjuan J , de Frutos R , Bramon E , Vassos E , Fraser G , Ettinger U , Picchioni M , Walker N , Toulopoulou T , Need AC , Ge D , Yoon JL , Shianna KV , Freimer NB , Cantor RM , Murray R , Kong A , Golimbet V , Carracedo A , Arango C , Costas J , Jonsson EG , Terenius L , Agartz I , Petursson H , Nothen MM , Rietschel M , Matthews PM , Muglia P , Peltonen L , St Clair D , Goldstein DB , Stefansson K , Collier DA
Ref : Nature , 460 :744 , 2009
Abstract : Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
ESTHER : Stefansson_2009_Nature_460_744
PubMedSearch : Stefansson_2009_Nature_460_744
PubMedID: 19571808

Title : A role for the acetylcholine receptor-inducing protein ARIA in oligodendrocyte development - Vartanian_1994_Proc.Natl.Acad.Sci.U.S.A_91_11626
Author(s) : Vartanian T , Corfas G , Li Y , Fischbach GD , Stefansson K
Ref : Proc Natl Acad Sci U S A , 91 :11626 , 1994
Abstract : ARIA acetylcholine receptor-inducing activity protein, is a member of a family of ligands that includes the Neu differentiation factor, heregulin, and glial growth factor. These ligands all act through one or more receptor tyrosine kinases of approximately 185 kDa. In some conditions these ligands promote proliferation, whereas in others they induce differentiation. ARIA was originally isolated from chick brain on the basis of its ability to induce synthesis of nicotinic acetylcholine receptors in skeletal muscle. In this paper we show that ARIA is expressed in the subventricular zone of the rat brain and that it enhances the development of oligodendrocytes from bipotential (O2A) glial progenitor cells. We have also found that ARIA induces tyrosine phosphorylation of a 185-kDa protein in O2A progenitor cells. ARIA does not increase bromodeoxyuridine incorporation by oligodendrocytes but is mitogenic when added to Schwann cells in vitro. Thus, ARIA accelerates the formation of oligodendrocytes in vitro and is expressed where it could exercise the same influence in vivo.
ESTHER : Vartanian_1994_Proc.Natl.Acad.Sci.U.S.A_91_11626
PubMedSearch : Vartanian_1994_Proc.Natl.Acad.Sci.U.S.A_91_11626
PubMedID: 7526399