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




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

PublisherNATURE PUBLISHING GROUP

2016

Nature Communications

NATURE COMMUNICATIONS

NAT COMMUN

ARTN 13357

7

11

2041-1723

DOIhttps://doi.org/10.1038/ncomms13357



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.

Last updated on 2024-26-11 at 12:20