Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.

Research output: Contribution to journalLetter

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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. / Zheng, Hou-Feng; Forgetta, Vincenzo; Hsu, Yi-Hsiang; Estrada, Karol; Rosello-Diez, Alberto; Leo, Paul J; Dahia, Chitra L; Park-Min, Kyung Hyun; Tobias, Jonathan H; Kooperberg, Charles; Kleinman, Aaron; Styrkarsdottir, Unnur; Liu, Ching-Ti; Uggla, Charlotta; Evans, Daniel S; Nielson, Carrie M; Walter, Klaudia; Pettersson-Kymmer, Ulrika; McCarthy, Shane; Eriksson, Joel; Kwan, Tony; Jhamai, Mila; Trajanoska, Katerina; Memari, Yasin; Min, Josine; Huang, Jie; Danecek, Petr; Wilmot, Beth; Li, Rui; Chou, Wen-Chi; Mokry, Lauren E; Moayyeri, Alireza; Claussnitzer, Melina; Cheng, Chia-Ho; Cheung, Warren; Medina-Gómez, Carolina; Ge, Bing; Chen, Shu-Huang; Choi, Kwangbom; Oei, Ling; Fraser, James; Kraaij, Robert; Hibbs, Matthew A; Gregson, Celia L; Paquette, Denis; Hofman, Albert; Wibom, Carl; Tranah, Gregory J; Marshall, Mhairi; Gardiner, Brooke B; Cremin, Katie; Auer, Paul; Hsu, Li; Ring, Sue; Tung, Joyce Y; Thorleifsson, Gudmar; Enneman, Anke W; van Schoor, Natasja M; de Groot, Lisette C P G M; van der Velde, Nathalie; Melin, Beatrice; Kemp, John P; Christiansen, Claus; Sayers, Adrian; Zhou, Yanhua; Calderari, Sophie; van Rooij, Jeroen; Carlson, Chris; Peters, Ulrike; Berlivet, Soizik; Dostie, Josée; Uitterlinden, Andre G; Williams, Stephen R; Farber, Charles; Grinberg, Daniel; LaCroix, Andrea Z; Haessler, Jeff; Chasman, Daniel I; Giulianini, Franco; Rose, Lynda M; Ridker, Paul M; Eisman, John A; Nguyen, Tuan V; Center, Jacqueline R; Nogues, Xavier; Garcia-Giralt, Natalia; Launer, Lenore L; Gudnason, Vilmunder; Mellström, Dan; Vandenput, Liesbeth; Amin, Najaf; van Duijn, Cornelia M; Karlsson, Magnus; Ljunggren, Östen; Svensson, Olle; Hallmans, Göran; Rousseau, François; Giroux, Sylvie; Bussière, Johanne; Arp, Pascal P; Koromani, Fjorda; Prince, Richard L; Lewis, Joshua R; Langdahl, Bente L; Pernille Hermann, A; Jensen, Jens-Erik B; Kaptoge, Stephen; Khaw, Kay-Tee; Reeve, Jonathan; Formosa, Melissa M; Xuereb-Anastasi, Angela; Åkesson, Kristina; McGuigan, Fiona; Garg, Gaurav; Olmos, Jose M; Zarrabeitia, Maria T; Riancho, Jose A; Ralston, Stuart H; Alonso, Nerea; Jiang, Xi; Goltzman, David; Pastinen, Tomi; Grundberg, Elin; Gauguier, Dominique; Orwoll, Eric S; Karasik, David; Davey-Smith, George; Smith, Albert V; Siggeirsdottir, Kristin; Harris, Tamara B; Carola Zillikens, M; van Meurs, Joyce B J; Thorsteinsdottir, Unnur; Maurano, Matthew T; Timpson, Nicholas J; Soranzo, Nicole; Durbin, Richard; Wilson, Scott G; Ntzani, Evangelia E; Brown, Matthew A; Stefansson, Kari; Hinds, David A; Spector, Tim; Adrienne Cupples, L; Ohlsson, Claes; Greenwood, Celia M T; Jackson, Rebecca D; Rowe, David W; Loomis, Cynthia A; Evans, David M; Ackert-Bicknell, Cheryl L; Joyner, Alexandra L; Duncan, Emma L; Kiel, Douglas P; Rivadeneira, Fernando; Richards, J Brent.

In: Nature, Vol. 526, No. 7571, 2015, p. 112-117.

Research output: Contribution to journalLetter

Harvard

Zheng, H-F, Forgetta, V, Hsu, Y-H, Estrada, K, Rosello-Diez, A, Leo, PJ, Dahia, CL, Park-Min, KH, Tobias, JH, Kooperberg, C, Kleinman, A, Styrkarsdottir, U, Liu, C-T, Uggla, C, Evans, DS, Nielson, CM, Walter, K, Pettersson-Kymmer, U, McCarthy, S, Eriksson, J, Kwan, T, Jhamai, M, Trajanoska, K, Memari, Y, Min, J, Huang, J, Danecek, P, Wilmot, B, Li, R, Chou, W-C, Mokry, LE, Moayyeri, A, Claussnitzer, M, Cheng, C-H, Cheung, W, Medina-Gómez, C, Ge, B, Chen, S-H, Choi, K, Oei, L, Fraser, J, Kraaij, R, Hibbs, MA, Gregson, CL, Paquette, D, Hofman, A, Wibom, C, Tranah, GJ, Marshall, M, Gardiner, BB, Cremin, K, Auer, P, Hsu, L, Ring, S, Tung, JY, Thorleifsson, G, Enneman, AW, van Schoor, NM, de Groot, LCPGM, van der Velde, N, Melin, B, Kemp, JP, Christiansen, C, Sayers, A, Zhou, Y, Calderari, S, van Rooij, J, Carlson, C, Peters, U, Berlivet, S, Dostie, J, Uitterlinden, AG, Williams, SR, Farber, C, Grinberg, D, LaCroix, AZ, Haessler, J, Chasman, DI, Giulianini, F, Rose, LM, Ridker, PM, Eisman, JA, Nguyen, TV, Center, JR, Nogues, X, Garcia-Giralt, N, Launer, LL, Gudnason, V, Mellström, D, Vandenput, L, Amin, N, van Duijn, CM, Karlsson, M, Ljunggren, Ö, Svensson, O, Hallmans, G, Rousseau, F, Giroux, S, Bussière, J, Arp, PP, Koromani, F, Prince, RL, Lewis, JR, Langdahl, BL, Pernille Hermann, A, Jensen, J-EB, Kaptoge, S, Khaw, K-T, Reeve, J, Formosa, MM, Xuereb-Anastasi, A, Åkesson, K, McGuigan, F, Garg, G, Olmos, JM, Zarrabeitia, MT, Riancho, JA, Ralston, SH, Alonso, N, Jiang, X, Goltzman, D, Pastinen, T, Grundberg, E, Gauguier, D, Orwoll, ES, Karasik, D, Davey-Smith, G, Smith, AV, Siggeirsdottir, K, Harris, TB, Carola Zillikens, M, van Meurs, JBJ, Thorsteinsdottir, U, Maurano, MT, Timpson, NJ, Soranzo, N, Durbin, R, Wilson, SG, Ntzani, EE, Brown, MA, Stefansson, K, Hinds, DA, Spector, T, Adrienne Cupples, L, Ohlsson, C, Greenwood, CMT, Jackson, RD, Rowe, DW, Loomis, CA, Evans, DM, Ackert-Bicknell, CL, Joyner, AL, Duncan, EL, Kiel, DP, Rivadeneira, F & Richards, JB 2015, 'Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.', Nature, vol. 526, no. 7571, pp. 112-117. https://doi.org/10.1038/nature14878

APA

Zheng, H-F., Forgetta, V., Hsu, Y-H., Estrada, K., Rosello-Diez, A., Leo, P. J., ... Richards, J. B. (2015). Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature, 526(7571), 112-117. https://doi.org/10.1038/nature14878

CBE

Zheng H-F, Forgetta V, Hsu Y-H, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu C-T, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, McCarthy S, Eriksson J, Kwan T, Jhamai M, Trajanoska K, Memari Y, Min J, Huang J, Danecek P, Wilmot B, Li R, Chou W-C, Mokry LE, Moayyeri A, Claussnitzer M, Cheng C-H, Cheung W, Medina-Gómez C, Ge B, Chen S-H, Choi K, Oei L, Fraser J, Kraaij R, Hibbs MA, Gregson CL, Paquette D, Hofman A, Wibom C, Tranah GJ, Marshall M, Gardiner BB, Cremin K, Auer P, Hsu L, Ring S, Tung JY, Thorleifsson G, Enneman AW, van Schoor NM, de Groot LCPGM, van der Velde N, Melin B, Kemp JP, Christiansen C, Sayers A, Zhou Y, Calderari S, van Rooij J, Carlson C, Peters U, Berlivet S, Dostie J, Uitterlinden AG, Williams SR, Farber C, Grinberg D, LaCroix AZ, Haessler J, Chasman DI, Giulianini F, Rose LM, Ridker PM, Eisman JA, Nguyen TV, Center JR, Nogues X, Garcia-Giralt N, Launer LL, Gudnason V, Mellström D, Vandenput L, Amin N, van Duijn CM, Karlsson M, Ljunggren Ö, Svensson O, Hallmans G, Rousseau F, Giroux S, Bussière J, Arp PP, Koromani F, Prince RL, Lewis JR, Langdahl BL, Pernille Hermann A, Jensen J-EB, Kaptoge S, Khaw K-T, Reeve J, Formosa MM, Xuereb-Anastasi A, Åkesson K, McGuigan F, Garg G, Olmos JM, Zarrabeitia MT, Riancho JA, Ralston SH, Alonso N, Jiang X, Goltzman D, Pastinen T, Grundberg E, Gauguier D, Orwoll ES, Karasik D, Davey-Smith G, Smith AV, Siggeirsdottir K, Harris TB, Carola Zillikens M, van Meurs JBJ, Thorsteinsdottir U, Maurano MT, Timpson NJ, Soranzo N, Durbin R, Wilson SG, Ntzani EE, Brown MA, Stefansson K, Hinds DA, Spector T, Adrienne Cupples L, Ohlsson C, Greenwood CMT, Jackson RD, Rowe DW, Loomis CA, Evans DM, Ackert-Bicknell CL, Joyner AL, Duncan EL, Kiel DP, Rivadeneira F, Richards JB. 2015. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature. 526(7571):112-117. https://doi.org/10.1038/nature14878

MLA

Vancouver

Zheng H-F, Forgetta V, Hsu Y-H, Estrada K, Rosello-Diez A, Leo PJ et al. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature. 2015;526(7571):112-117. https://doi.org/10.1038/nature14878

Author

Zheng, Hou-Feng ; Forgetta, Vincenzo ; Hsu, Yi-Hsiang ; Estrada, Karol ; Rosello-Diez, Alberto ; Leo, Paul J ; Dahia, Chitra L ; Park-Min, Kyung Hyun ; Tobias, Jonathan H ; Kooperberg, Charles ; Kleinman, Aaron ; Styrkarsdottir, Unnur ; Liu, Ching-Ti ; Uggla, Charlotta ; Evans, Daniel S ; Nielson, Carrie M ; Walter, Klaudia ; Pettersson-Kymmer, Ulrika ; McCarthy, Shane ; Eriksson, Joel ; Kwan, Tony ; Jhamai, Mila ; Trajanoska, Katerina ; Memari, Yasin ; Min, Josine ; Huang, Jie ; Danecek, Petr ; Wilmot, Beth ; Li, Rui ; Chou, Wen-Chi ; Mokry, Lauren E ; Moayyeri, Alireza ; Claussnitzer, Melina ; Cheng, Chia-Ho ; Cheung, Warren ; Medina-Gómez, Carolina ; Ge, Bing ; Chen, Shu-Huang ; Choi, Kwangbom ; Oei, Ling ; Fraser, James ; Kraaij, Robert ; Hibbs, Matthew A ; Gregson, Celia L ; Paquette, Denis ; Hofman, Albert ; Wibom, Carl ; Tranah, Gregory J ; Marshall, Mhairi ; Gardiner, Brooke B ; Cremin, Katie ; Auer, Paul ; Hsu, Li ; Ring, Sue ; Tung, Joyce Y ; Thorleifsson, Gudmar ; Enneman, Anke W ; van Schoor, Natasja M ; de Groot, Lisette C P G M ; van der Velde, Nathalie ; Melin, Beatrice ; Kemp, John P ; Christiansen, Claus ; Sayers, Adrian ; Zhou, Yanhua ; Calderari, Sophie ; van Rooij, Jeroen ; Carlson, Chris ; Peters, Ulrike ; Berlivet, Soizik ; Dostie, Josée ; Uitterlinden, Andre G ; Williams, Stephen R ; Farber, Charles ; Grinberg, Daniel ; LaCroix, Andrea Z ; Haessler, Jeff ; Chasman, Daniel I ; Giulianini, Franco ; Rose, Lynda M ; Ridker, Paul M ; Eisman, John A ; Nguyen, Tuan V ; Center, Jacqueline R ; Nogues, Xavier ; Garcia-Giralt, Natalia ; Launer, Lenore L ; Gudnason, Vilmunder ; Mellström, Dan ; Vandenput, Liesbeth ; Amin, Najaf ; van Duijn, Cornelia M ; Karlsson, Magnus ; Ljunggren, Östen ; Svensson, Olle ; Hallmans, Göran ; Rousseau, François ; Giroux, Sylvie ; Bussière, Johanne ; Arp, Pascal P ; Koromani, Fjorda ; Prince, Richard L ; Lewis, Joshua R ; Langdahl, Bente L ; Pernille Hermann, A ; Jensen, Jens-Erik B ; Kaptoge, Stephen ; Khaw, Kay-Tee ; Reeve, Jonathan ; Formosa, Melissa M ; Xuereb-Anastasi, Angela ; Åkesson, Kristina ; McGuigan, Fiona ; Garg, Gaurav ; Olmos, Jose M ; Zarrabeitia, Maria T ; Riancho, Jose A ; Ralston, Stuart H ; Alonso, Nerea ; Jiang, Xi ; Goltzman, David ; Pastinen, Tomi ; Grundberg, Elin ; Gauguier, Dominique ; Orwoll, Eric S ; Karasik, David ; Davey-Smith, George ; Smith, Albert V ; Siggeirsdottir, Kristin ; Harris, Tamara B ; Carola Zillikens, M ; van Meurs, Joyce B J ; Thorsteinsdottir, Unnur ; Maurano, Matthew T ; Timpson, Nicholas J ; Soranzo, Nicole ; Durbin, Richard ; Wilson, Scott G ; Ntzani, Evangelia E ; Brown, Matthew A ; Stefansson, Kari ; Hinds, David A ; Spector, Tim ; Adrienne Cupples, L ; Ohlsson, Claes ; Greenwood, Celia M T ; Jackson, Rebecca D ; Rowe, David W ; Loomis, Cynthia A ; Evans, David M ; Ackert-Bicknell, Cheryl L ; Joyner, Alexandra L ; Duncan, Emma L ; Kiel, Douglas P ; Rivadeneira, Fernando ; Richards, J Brent. / Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. In: Nature. 2015 ; Vol. 526, No. 7571. pp. 112-117.

RIS

TY - JOUR

T1 - Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.

AU - Zheng, Hou-Feng

AU - Forgetta, Vincenzo

AU - Hsu, Yi-Hsiang

AU - Estrada, Karol

AU - Rosello-Diez, Alberto

AU - Leo, Paul J

AU - Dahia, Chitra L

AU - Park-Min, Kyung Hyun

AU - Tobias, Jonathan H

AU - Kooperberg, Charles

AU - Kleinman, Aaron

AU - Styrkarsdottir, Unnur

AU - Liu, Ching-Ti

AU - Uggla, Charlotta

AU - Evans, Daniel S

AU - Nielson, Carrie M

AU - Walter, Klaudia

AU - Pettersson-Kymmer, Ulrika

AU - McCarthy, Shane

AU - Eriksson, Joel

AU - Kwan, Tony

AU - Jhamai, Mila

AU - Trajanoska, Katerina

AU - Memari, Yasin

AU - Min, Josine

AU - Huang, Jie

AU - Danecek, Petr

AU - Wilmot, Beth

AU - Li, Rui

AU - Chou, Wen-Chi

AU - Mokry, Lauren E

AU - Moayyeri, Alireza

AU - Claussnitzer, Melina

AU - Cheng, Chia-Ho

AU - Cheung, Warren

AU - Medina-Gómez, Carolina

AU - Ge, Bing

AU - Chen, Shu-Huang

AU - Choi, Kwangbom

AU - Oei, Ling

AU - Fraser, James

AU - Kraaij, Robert

AU - Hibbs, Matthew A

AU - Gregson, Celia L

AU - Paquette, Denis

AU - Hofman, Albert

AU - Wibom, Carl

AU - Tranah, Gregory J

AU - Marshall, Mhairi

AU - Gardiner, Brooke B

AU - Cremin, Katie

AU - Auer, Paul

AU - Hsu, Li

AU - Ring, Sue

AU - Tung, Joyce Y

AU - Thorleifsson, Gudmar

AU - Enneman, Anke W

AU - van Schoor, Natasja M

AU - de Groot, Lisette C P G M

AU - van der Velde, Nathalie

AU - Melin, Beatrice

AU - Kemp, John P

AU - Christiansen, Claus

AU - Sayers, Adrian

AU - Zhou, Yanhua

AU - Calderari, Sophie

AU - van Rooij, Jeroen

AU - Carlson, Chris

AU - Peters, Ulrike

AU - Berlivet, Soizik

AU - Dostie, Josée

AU - Uitterlinden, Andre G

AU - Williams, Stephen R

AU - Farber, Charles

AU - Grinberg, Daniel

AU - LaCroix, Andrea Z

AU - Haessler, Jeff

AU - Chasman, Daniel I

AU - Giulianini, Franco

AU - Rose, Lynda M

AU - Ridker, Paul M

AU - Eisman, John A

AU - Nguyen, Tuan V

AU - Center, Jacqueline R

AU - Nogues, Xavier

AU - Garcia-Giralt, Natalia

AU - Launer, Lenore L

AU - Gudnason, Vilmunder

AU - Mellström, Dan

AU - Vandenput, Liesbeth

AU - Amin, Najaf

AU - van Duijn, Cornelia M

AU - Karlsson, Magnus

AU - Ljunggren, Östen

AU - Svensson, Olle

AU - Hallmans, Göran

AU - Rousseau, François

AU - Giroux, Sylvie

AU - Bussière, Johanne

AU - Arp, Pascal P

AU - Koromani, Fjorda

AU - Prince, Richard L

AU - Lewis, Joshua R

AU - Langdahl, Bente L

AU - Pernille Hermann, A

AU - Jensen, Jens-Erik B

AU - Kaptoge, Stephen

AU - Khaw, Kay-Tee

AU - Reeve, Jonathan

AU - Formosa, Melissa M

AU - Xuereb-Anastasi, Angela

AU - Åkesson, Kristina

AU - McGuigan, Fiona

AU - Garg, Gaurav

AU - Olmos, Jose M

AU - Zarrabeitia, Maria T

AU - Riancho, Jose A

AU - Ralston, Stuart H

AU - Alonso, Nerea

AU - Jiang, Xi

AU - Goltzman, David

AU - Pastinen, Tomi

AU - Grundberg, Elin

AU - Gauguier, Dominique

AU - Orwoll, Eric S

AU - Karasik, David

AU - Davey-Smith, George

AU - Smith, Albert V

AU - Siggeirsdottir, Kristin

AU - Harris, Tamara B

AU - Carola Zillikens, M

AU - van Meurs, Joyce B J

AU - Thorsteinsdottir, Unnur

AU - Maurano, Matthew T

AU - Timpson, Nicholas J

AU - Soranzo, Nicole

AU - Durbin, Richard

AU - Wilson, Scott G

AU - Ntzani, Evangelia E

AU - Brown, Matthew A

AU - Stefansson, Kari

AU - Hinds, David A

AU - Spector, Tim

AU - Adrienne Cupples, L

AU - Ohlsson, Claes

AU - Greenwood, Celia M T

AU - Jackson, Rebecca D

AU - Rowe, David W

AU - Loomis, Cynthia A

AU - Evans, David M

AU - Ackert-Bicknell, Cheryl L

AU - Joyner, Alexandra L

AU - Duncan, Emma L

AU - Kiel, Douglas P

AU - Rivadeneira, Fernando

AU - Richards, J Brent

PY - 2015

Y1 - 2015

N2 - The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

AB - The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

U2 - 10.1038/nature14878

DO - 10.1038/nature14878

M3 - Letter

VL - 526

SP - 112

EP - 117

JO - Nature

T2 - Nature

JF - Nature

SN - 0028-0836

IS - 7571

ER -