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
A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
NATURE PUBLISHING GROUP
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042716184
https://urn.fi/URN:NBN:fi-fe2021042716184
Tiivistelmä
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 combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
Kokoelmat
- Rinnakkaistallenteet [19207]