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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Schwarz PEH; Zhao JH; Eriksson JG; Kinnunen L; Luan JA; Raitakari OT; Kooner JS; Hassinen M; Ribel-Madsen R; Feitosa MF; Abecasis GR; Mangino M; Kanoni S; Chu AY; Wild SH; Milani L; Pankow JS; Medina-Gomez C; Oostra BA; Boehnke M; Goel A; Beilby J; Wong A; Prokopenko I; Pedersen O; Polasek O; Grewal J; Morris AP; Kajantie E; Perola M; Peters A; Hysi PG; Jokinen E; Spector TD; Mills R; Muller-Nurasyid M; Kutalik Z; Vitart V; Ohlsson C; Walker RW; Bellis C; Hui JN; Viikari JS; Justesen JM; Friedrich N; Albrecht E; Lahti J; Southam L; Tsafantakis E; Lichtner P; Hayward C; Rankinen T; Thorleifsson G; Mohlke KL; Willemsen G; Lakka TA; Hastie N; Husemoen LL; Chasman DI; McArdle WL; Watkins H; Mcknight B; Metspalu A; Palotie A; North KE; Scott RA; Cupples LA; Venturini C; Grarup N; Bragg-Gresham JL; Laitinen T; Teumer A; Ryan KA; Isaacs A; Njolstad I; Rauramaa R; Grassler J; Khaw KT; van der Harst P; Mannisto S; Salvi E; Graff M; Uitterlinden AG; Loos RJF; Bluher M; Hattersley AT; Esko T; Wang SR; Schlessinger D; Huffman JE; Kooner IK; Montasser ME; Willems SM; Bouchard C; van der Most PJ; Kolcic I; Tuomilehto J; Chambers JC; Boomsma DI; Bornstein SR; Pilia MG; Gieger C; Grallert H; Rao DC; Forouhi NG; Hansen T; Lewin AM; Heid IM; Blangero J; Palmer LJ; Fox C; Chines PS; Tonjes A; Hveem K; Penninx BW; Bonnycastle LL; Bruinenberg M; Vohl MC; Wilsgaard T; Stringham HM; Kovacs P; Oldehinkel AJ; Jarvelin MR; Ong KK; Hillege H; Harder MN; Stancakova A; Tachmazidou I; Strauch K; Monda KL; Doring A; Jackson AU; Hamsten A; Bakker SJL; Steinthorsdottir V; van Dongen J; Bergman RN; Bergmann S; Lindgren CM; Eklund N; Shudiner AR; Vartiainen E; Stefansson K; Smit JH; Van Vliet-Ostaptchouk JV; Kuusisto J; Musk AW; Lehtimaki T; Hartman CA; Frayling T; Thorsteinsdottir U; Qi L; Heliovaara M; Hottenga JJ; Salomaa V; Jorgensen T; Wright AF; Tremblay A; Knekt PB; Muller G; Holmen O; Lyssenko V; Kyriakou T; Volker U; Ferreira T; Jalilzadeh S; Jeff JM; Ridker PM; Gansevoort RT; Boerwinkle E; Borecki IB; D'Avila F; Hirschhorn JN; Magi R; Luben R; Sarzynski MA; Barlassina C; Kaplan RC; Cadby G; Ahluwalia TS; Zhang WH; Gjesing AP; Puolijoki H; Cusi D; Smith MT; Koskinen S; Widen E; Manunta P; Zillikens MC; Chiang CWK; Strachan DP; Rice TK; Winkler TW; Hofman A; Kristiansson K; Swertz MA; Koistinen HA; Sparso TH; Farrall M; Havulinna AS; Campbell H; Lindstrom J; Wilson JF; Snieder H; Sorensen TIA; Linneberg A; Uusitupa M; Dimitriou M; O'Connell JR; Eriksson J; Vollenweider P; Jula A; Zeggini E; Deloukas P; Dedoussis G; Farmaki AE; Langenberg C; Scholtens S; van Duijn CM; Mahajan A; Bartz TM; Richards M; Psaty BM; Rivadeneira F; Vandenput L; Justice AE; Cucca F; Hunter DJ; Fischer K; Jousilahti P; Homuth G; Vonk JM; Mihailov E; Perusse L; Sebert S; McCarthy MI; Heard-Costa NL; Leach IM; Nolte IM; Wareham NJ; Yerges-Armstrong LM; Ried JS; Karaleftheri M; Pramstaller PP; Pichler I; Stolk RP; Groop LC; James AL; Swift AJ; Glorioso N; Verweij N; Rose LM; Waeber G; Narisu N; Sung YJ; Rayner NW; Collins FS; Lorbeer R; Hicks AA; Sanna S; Laakso M; Chen YDI; Stirrups K; Osmond C; Paternoster L; Lorentzon M; Ittermann T; Rudan I; Hu F; de Geus EJC; Kahonen M; Gorski M; Stumvoll M; Alves AC; Kuh D; Keinanen-Kiukaanniemi SM

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a ...

Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals

Jylhava J; Kahonen M; Jylha M; Marttila S; Kananen L; Hervonen A; Nevalainen T; Mononen N; Hurme M; Raitakari OT; Lehtimaki T

Background: Human aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an ...

NAFLD risk alleles in PNPLA3, TM6SF2, GCKR and LYPLAL1 show divergent metabolic effects

Kettunen J; Kangas AJ; Raitakari OT; Soininen P; Viikari J; Wurtz P; Lehtimaki T; Sliz E; Ala-Korpela M; Sebert S; Kahonen M; Mannikko M

Fatty liver has been associated with unfavourable metabolic changes in circulation. To provide insights in fatty liver-related metabolic deviations, we compared metabolic association profile of fatty liver versus metabolic ...

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects

Horikoshi M; Granell R; Lichtenstein P; Kemp JP; Gilliland F; Custovic A; Henriksen TB; Mook-Kanamori DO; Santa-Marina L; Boomsma DI; Ahluwalia TS; Cavadino A; Strandberg T; Freathy RM; Snieder H; van der Most PJ; Myhre R; Larsson H; Najman JM; Eliasen AU; Almgren P; Beaumont RN; Geller F; Kaprio J; McCarthy MI; Fadista J; Lawlor DA; Frayling TM; Melbye M; St Pourcain B; Hadley D; Hypponen E; Cooper C; Feenstra B; Warrington NM; Panoutsopoulou K; Zemel BS; Liu J; Prasad RB; Cousminer DL; Coin L; Day FR; Lappe JM; Raikkonen K; Pitkanen N; Gauderman WJ; Bond T; Schnurr TM; Korner A; Xu CJ; Magnus P; Lowe WL; Grant SFA; Scott JG; Rivadeneira F; O'Reilly P; Uitterlinden AG; Morris AP; Hayes MG; Holloway JW; Yaghootkar H; Hottenga JJ; Ntalla I; Tyrrell J; Liu XP; Heinrich J; Hattersley AT; Stoltenberg C; Power C; Simpson A; Iniguez C; Kalkwarf HJ; Holt P; Koppelman GH; Middeldorp CM; Wang CA; Ong KK; Lyytikainen LP; Jarvelin MR; Henders AK; Williams GM; Kutalik Z; Standl M; Sorensen TIA; Chen ZH; Paternoster L; Vogelezang S; Yi L; Linneberg A; Sleiman PMM; Bustamante M; Hocher B; Gaillard R; Vuoksimaa E; Lundstrom S; Mahajan A; Timpson NJ; Kumar A; Bradfield JP; Davies GE; Ma RCW; Mace A; Lewin AM; Felix JF; Viikari J; Nolte IM; Watkins WJ; Xu SJ; van Beijsterveldt T; Atalay M; Teo YY; Hakonarson H; Pulkkinen L; Widen EE; Smith GD; Wray NR; Palviainen T; Richmond RC; Mamun AA; Willemsen G; Hartman CA; Melen E; Oberfield SE; Medland SE; Li J; Rose RJ; Ahlqvist E; Eriksson JG; Ang W; Hebebrand J; Das S; McCarthy NS; Kerkhof M; Johansson S; Mannikko M; Duijts L; Bilbao JR; Tiemeier H; Bartels M; Pahkala K; Sebert S; Grarup N; Hirschhorn JN; Sunyer J; Lindi V; Pershagen G; Bonnelykke K; Reynolds RM; Vonk JM; Fedko IO; Borja JB; Charoen P; Eastwood PR; Dedoussis GV; Plomin R; Kulohoma B; Wilson JF; Pennell CE; Kotecha S; Lakka TA; Vrijkotte TGM; Vilor-Tejedor N; Rodriguez A; Adair LS; Oldehinkel AJ; Morgen CS; Salem R; Torrent M; Hinney A; Zeggini E; Tiemeier HN; Groop L; Nohr EA; Kahonen M; Kreiner-Moller E; Selzam S; Strachan DP; Taylor M; Hivert MF; Helgeland O; Karhunen V; Wichmann HE; Robertson NR; Sleiman PMA; Steegers EAP; Lindgren CM; Henderson J; Evans DM; Prokopenko I; Guxens M; Oken E; Murray JC; Gilsanz V; Straker L; Bisgaard H; Auvinen J; Lehtimaki T; Raitakari OT; Mbarek H; Hansen T; Estivill X; Jacobsson B; Curtin JA; Jugessur A; Thiering E; Whitehouse AJO; De Silva NM; Pedersen O; Skotte L; Perry JRB; Magi R; Elliott P; Martin NG; Nivard MG; Mohlke KL; Njolstad PR; Beckmann JS; Monnereau C; Jaddoe VWV; Zafarmand MH; Saw SM; van Duijn CM; Shepherd JA; Lahti J

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as ...

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

de Mutsert R; Kritchevsky SB; Heng CK; Vollenweider P; Howard BV; Wong TY; Samani NJ; Tai ES; Dorajoo R; Wu TC; He J; Jonas JB; Scott J; Guo XQ; Li CW; Rose LM; Bowden DW; Gasparini P; Alver M; Kahonen M; Rice K; van Duijn CM; Khor CC; Fau JD; Scott RA; Bartz TM; Sidney S; Fuentes LDL; Warren HR; Ehret G; Smith JA; Penninx BWJH; Wang YJ; Froguel P; Zonderman AB; Lehtimaki T; Hallmans G; Campbell A; Bin Wei W; Province MA; Kooperberg C; Palmas W; Leander K; Kubo M; Stancakova A; Zhu XF; Rankinen T; Boehnke M; Mohlke KL; Elliott P; Watkins H; Raffel LJ; Tham YC; Harris TB; Hagenaars SP; Poiasek O; Nelson CP; Wickremasinghe AR; Vojinovic D; Aschard H; Gieger C; Smith AV; Scott WR; Yu CZ; Winkler TW; O'Connell JR; Koh WP; Cheng CY; Munroe PB; Kutalik Z; Porteous DJ; Marten J; Laurie CC; Heikkinen S; Vitart V; Brumat M; Charumathi S; Ntalla I; Lewis CE; Afaq S; van Dam RM; Gao C; Varga TV; Broeckel U; Magnusson PKE; Feitosa MF; Boerwinkle E; Uitterlinden AG; Deng X; Loh M; Ware EB; Rao DC; Lakka TA; Snieder H; Louie T; Komulainen P; Lin S; Wang LH; Eppinga RN; Perls T; Brown M; Manning AK; Gudnason V; McKenzie CA; Mook-Kanamori DO; Yuan JM; Meitinger T; Hirata M; Yao J; Fisher V; Hartwig FP; Horta BL; Sims M; Burke GL; Momozawa Y; Waldenberger M; Morrison AC; Chambers JC; Li YZ; Eaton CB; Richard MA; Amin N; Freedman BI; Franks PW; Robino A; Langenberg C; Teo YY; Schmidt CO; Takeuchi F; Farrall M; Norris JM; Chakravarti A; Borecki I; Padmanabhan S; Chen X; Sim XL; Ridker PM; Franco OH; Rosendaal FR; Magi R; Liu YM; Launer LJ; van der Harst P; Bielak LF; Rueedi R; Roll K; Zheng W; Wagenknecht LE; Rauramaa R; Harris SE; Felix SB; Weir DR; Sofer T; Caulfield MJ; Kamatani Y; Nolte IM; van der Most PJ; Langefeld CD; Peyser PA; Tan NYQ; Franceschini N; Peters A; Said MA; Nalls MA; Kraja AT; Raitakari OT; Gao H; John U; Gigante B; Christensen K; Divers J; Kuusisto J; Fornage M; Katsuya T; Poulter N; Fox ER; Starr JM; Chen YDI; Milaneschi Y; Evangelou E; Rotter JI; Deary IJ; Luan J; Wen WQ; Liu JJ; Kato N; Kilpelainen TO; Evans MK; Kooner JS; Wojczynski MK; Wang YX; Milani L; Arking DE; Gandin I; Hsu FC; Rotimi CN; Schreiner PJ; Becker DM; Tang H; Tayo BO; Gauderman WJ; Sitlani CM; Schupf N; Weiss S; Gu DF; Laakso M; Stringham HM; Palmer ND; Williams C; Wareham NJ; Kuhnel B; Musani SK; Levy D; Cai QY; Goel A; Sotoodehnia N; Friedlander Y; Ghanbari M; Zhao W; Ding J; Liu JM; Canouil M; Psaty BM; Pereira AC; Lehne B; Brown MR; Shu XO; Riaz M; Connell JM; Chasman DI; Kelly TN; Cupples LA; Taylor KD; de Silva HJ; Chai JF; Duan Q; Krieger JE; Strauch K; Kasturiratne A; Turner ST; Lohman KK; Forouhi NG; He MI; Zhang WH; Horimoto ARVR; Amini M; Ikram MA; Tajuddin SM; Esko T; Gu CC; Jackson AU; Sever PS; Kardia SLR; Noordam R; Pedersen NL; Correa A; Metspalu A; Hagemeijer Y; Matoba N; Boissel M; Forrester T; Hayward C; Shi Y; Bentley AR; Oldehinkel AJ; Sung YJ; Study LC; Schwander K; Laguzzi F; Bouchard C; Aung T; Yanek LR; Zhao JH

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association ...

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Winsvold BS; Sigurdardottir GR; Kahonen M; Ran C; Kurth T; Farkkila M; Belin AC; Gormley P; Sveinsson OA; Ripatti S; Hrafnsdottir MG; Magnusson SH; Widen E; Aromaa A; van Dijk KW; Rosendaal FR; Ullum H; Buring JE; de Boer I; Skogholt AH; Ikram MA; Banasik K; Hautakangas H; Hottenga JJ; Nyholt DR; Noordam R; Dichgans M; Thomas LF; Wessman M; Chalmer MA; van den Maagdenberg AMJM; Freilinger T; Olesen J; Kallela M; Thorgeirsson TE; Bjornsdottir A; Hveem K; Kogelman LJA; Zwart JA; Penninx BWJH; Raitakari OT; Stefansson K; Hansen TF; Burgdorf KS; Hagen K; Garbrielsen ME; Benner C; Johnsen MB; Pedersen OB; Harder AVE; Lighart L; Malik R; Ruotsalainen SE; Ghanbari M; Vijfhuizen LS; Kristoffersen ES; Lehtimaki T; Pelzer N; Ridker PM; Happola P; Jarvelin MR; Pirinen M; Chasman DI; Bjornsdottir G; Brumpton B; Terwindt GM; Boomsma DI; Erikstrup C; Stefansson H; Artto V; Palotie A

Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura ...

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Zemel BS; Iniguez C; Pedersen O; Koletzko B; Escribano J; Monnereau C; Uitterlinden AG; Bisgaard H; Atalay M; Froguel P; Curtin JA; Chesi A; Sly PD; Zeggini E; Heude B; Geller F; Freathy RM; Pennell CE; Horikoshi M; Viikari J; Grote V; Yengo L; Lyytikainen LP; Kuhnapfel A; Korner A; Holm JC; Hakonarson H; Verduci E; Gruszfeld D; Reischl E; Teo KK; Lehtimaki T; Bilbao JR; Bacelis J; Rivadeneira F; Beaumont RN; Reijneveld SA; Johansson S; Vonk JM; Lakka TA; Jarvelin MR; Morgen CS; Timpson NJ; Schnurr TM; Plomin R; Kirsten H; Eriksson JG; Ahluwalia TS; Thiering E; Pahkala K; van der Most PJ; Felix JF; Grarup N; Farooqi IS; Standl M; Simpson A; Groen-Blokhuis M; Bustamante M; Hattersley AT; Barroso I; Njolstad PR; Medina-Gomez C; Sebert S; Charles MA; Hottenga JJ; Lindi V; Raitakari O; Melbye M; Brown CD; Stergiakouli E; Vrijheid M; van Beijsterveldt CEM; Bradfield JP; Boomsma DI; Sunyer J; Zafarmand MH; Vilor-Tejedor N; Hypponen E; Scholz M; Vogel M; Jaddoe VWV; Holt PG; Heinrich J; Landgraf K; Closa-Monasterolo R; Custovic A; Dedoussis GD; Li AHL; Rzehak P; Hansen T; Helgeland O; Lind MV; Vaudel M; Cousminer DL; Snieder H; Alyass A; Joro R; Vrijkotte TGM; Grant SFA; Ntalla I; van Schaik BDC; Meyre D; Lowry E; Michaelsen KF; Hollensted M; Have CT; Stokholm J; Smith GD; Heiskala A; Koppelman GH; Selzam S; Kiess W; McCarthy MI; Knight BA; Beilin LJ; Nohr EA; Jacobsson B; Wheeler E; Panoutsopoulou K; Clement K; Nielsen TRH; Carstensen L; Feenstra B; Niinikoski H; Karhunen V; Sorensen TIA; Frithioff-Bojsoe C; Wang CRA; Chawes B; Bonnelykke K; Kahonen M; Torrent M; Langhendries JP; Vogelezang S; Fedko IO; Leinonen JT; Vinding RK; Power C; Ong K; Mori TA; Widen E; Murray C; Santa-Marina L; Pitkanen N; Oldehinkel AJ

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed ...

The relationship between temperament, polygenic score for intelligence and cognition: A population-based study of middle-aged adults

Dobewall H; Taittonen L; Jokinen E; Lehtimaki T; Cloninger CR; Raitakari O; Tolli P; Ravaja N; Pahkala K; Hutri-Kahonen N; Ahola-Olli A; Rovio S; Tossavainen P; Keltikangas-Jarvinen L; Laitinen TT; Saarinen A; Hintsanen M; Kahonen M

We investigated whether temperament modifies an association between polygenic intelligence potential and cognitive test performance in midlife. The participants (n = 1647, born between 1962 and 1977) were derived from the ...

Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study

Grote V; Koh WP; Lemaitre R; Raitakari O; Zhao W; Lecoeur C; Amouyel P; Sorensen TIA; Chavarro JE; Lai CQ; Mook-Kanamori DO; Khor CC; Kleber ME; Burkhardt R; Hansen T; Cooper C; Bisgaard H; Psaty BM; Yuan JM; Yu CZ; Schulz CA; YinWong T; Pahkala K; Inskip H; Gao M; Thiering E; Corella D; Zhang T; Meirhaeghe A; Rzehak P; Tjonneland A; Mohlke KL; Wang YJ; Wang CA; Mozaffarian D; Viikari J; Tiesler CMT; Balkau B; Noordam R; Voortman T; Crozier SR; Teo YY; Gruszfeld D; Fink NR; Jaddoe VV; Uitterlinden AG; van Heemst D; Franco OH; Kamatani Y; Sim XL; Pitkanen N; Vinding RK; Van Rooij FJA; Qi L; Felix JF; Gupta P; Gottrand F; Rosendaal FR; Wang TA; Ridker PM; He M; Ellervik C; Sonestedt E; van Dam R; Marouli E; Chasman DI; Koletzko B; Jameson K; Standl M; Verduci E; Dorajoo R; Shi Y; Delgado G; Escribano J; Hofman A; de Mutsert R; Mackey DA; Saw SM; Boreham CA; Cheng CY; Sabanayagam C; Bonnelykke K; Tucker KL; Akiyama M; Lehtimaki T; Tham YC; Godfrey KM; Langhendries JP; Rossing P; Kubo M; Loeffler M; Chai JF; Graff M; Zheng Y; Kahonen M; Ahluwalia TVS; Fang Z; Marz W; Lee NR; Orho-Melander M; Frazier-Wood A; Djousse L; Tai ES; Dallongeville J; Coltell O; Dennison E; Smith GD; Arnett DK; Scholz M; Niinikoski H; Hypponen E; Ordovas JM; Power C; Froguel P; North KE; Fumeron F; Huang T; Wu TC; Zhou A; Li X; Liu JJ; Overvad K; Estruch R; Sevelsted A; Moreno LA; Lim B; Deloukas P; Thiery J; Rivadeneira F; Pedersen O; Dedoussis G; Lim SH; Ericson U; Kilpelainen TO

IMPORTANCE Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations.OBJECTIVE To test the ...

A meta-analysis of genome-wide association studies identifies multiple longevity genes

van Duijn CM; van Der Spek A; Arnold AM; Cummings SR; Duncan R; Seppala I; Zeng Y; Uitterlinden AG; Jylha M; Jagger C; Smith J; Faul JD; Sorensen TIA; Orwoll ES; Perls TT; Rotter JI; Barzilai N; Sarnowski C; Psat BM; Debrabant B; Huisman M; Christensen K; Nohr EA; Robine JM; Blanche H; Tesi N; Liu XM; Province MA; Gudnaso V; Amin N; Ye K; Holstege H; Becker EJ; Slagboom PE; Weir D; Kahonen M; Deelen J; Lieb WG; van Der Flier W; Cordell HJ; Lehtimaki T; Smith AV; Wojczynski MK; Newman AB; Murabito JM; Kardia SLR; Atzmon G; Kirkwood TBL; Ayers KL; Nygaard M; Jansen I; van Der Lee SJ; Karasik D; Galan P; Cubaynes S; Christiansen L; Taylor KD; Deleuze JF; Vaupel JW; Dose J; Martin-Ruiz C; Launer LJ; Biggs ML; Sebastiani P; Franceschi C; Arking DE; Lyytikainen LP; Evans DS; Ware EB; Lunetta KL; Kiel DP; Min JX; Beekman M; van Heemst D; Collerton JC; Nebe A; Zheng WL; Nie C; Davies K; Raitakari OT; Kingston A; Hurme MA; Harris TB; Reinders MJT

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases ...