Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 199-209 |
| Number of pages | 11 |
| Journal | Nature Neuroscience |
| Volume | 18 |
| Issue number | 2 |
| Early online date | 19 Jan 2015 |
| DOIs | |
| Publication status | Published - Feb 2015 |
Access to Document
Fingerprint Dive into the research topics of 'Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways'. Together they form a unique fingerprint.
Profiles
-
Professor Stanley Zammit
- Bristol Medical School (PHS) - Professor of Psychiatry
- Bristol Population Health Science Institute
- Centre for Academic Mental Health
- Bristol Neuroscience
Person: Academic , Member
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. / O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H; Duncan, Laramie; Parikshak, Neelroop N; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M; Purcell, Shaun M; Posthuma, Danielle; Nurnberger, John I; Lee, S Hong; Faraone, Stephen V; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Buitelaar, Jan K; Bunney, William E; Buxbaum, Joseph D; Byerley, William F; Byrne, Enda M; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C Robert; Collier, David A; Cook, Edwin H; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H; Craig, David W; Craig, Ian W; Crosbie, Jennifer; Cuccaro, Michael L; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; Geus, Eco J De; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J; Doyle, Alysa E; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P; Edenberg, Howard J; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E; Ferrier, I Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Freedman, Robert; Freimer, Nelson B; Freitag, Christine M; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V; Georgieva, Lyudmila; Gershon, Elliot S; Giegling, Ina; Gill, Michael; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Greenwood, Tiffany A; Grice, Dorothy E; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; Haan, Lieuwe De; Haines, Jonathan L; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P; Hamshere, Marian Lindsay; Hansen, Thomas F; Hartmann, Annette M; Hautzinger, Martin; Heath, Andrew C; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J; Hottenga, Jouke-Jan; Hultman, Christina M; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G.; Jones, Ian R; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K; Kahn, René S; Kandaswamy, Radhika; Keller, Matthew C; Kennedy, James L; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George; Klauck, Sabine M; Klei, Lambertus; Knowles, James A.; Kohli, Martin A; Koller, Daniel L; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Längström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B; Leboyer, Marion; Ledbetter, David H; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F; Lewis, Cathryn M; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Liu, Chunyu; Lohoff, Falk W; Loo, Sandra K; Lord, Catherine; Lowe, Jennifer K; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela A F; Maestrini, Elena; Magnusson, Patrik K E; Mahon, Pamela B; Maier, Wolfgang; Malhotra, Anil K; Mane, Shrikant M; Martin, Christa L; Martin, Nicholas G; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A; McGhee, Kevin A; McGough, James J; McGrath, Patrick J; McGuffin, Peter; McInnis, Melvin G; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W; McMahon, Francis J; McMahon, William M; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P; Montgomery, Grant W; Moran, Jennifer L; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W; Morrow, Eric M; Escott-Price, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W; Muir, Walter J; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M; Myin-Germeys, Inez; Neale, Michael C; Nelson, Stan F; Nievergelt, Caroline M; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A; Nöthen, Markus M; Nwulia, Evaristus A; Nyholt, Dale R; Oades, Robert D; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A; Osby, Urban; Owen, Michael John; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N; Pato, Michele T; Penninx, Brenda W; Pergadia, Michele L; Pericak-Vance, Margaret A; Pickard, Benjamin S; Pimm, Jonathan; Piven, Joseph; Potash, James B; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J; Quinn, Emma M; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R; Sanders, Stephan J; Santangelo, Susan L; Sergeant, Joseph A; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F; Scheftner, William A; Schellenberg, Gerard D; Scherer, Stephen W; Schork, Nicholas J; Schulze, Thomas G; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J; Shi, Jianxin; Shilling, Paul D; Shyn, Stanley I; Silverman, Jeremy M; Slager, Susan L; Smalley, Susan L; Smit, Johannes H; Smith, Erin N; Sonuga-Barke, Edmund J S; Clair, David St.; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S; Strohmaier, Jana; Stroup, T Scott; Sutcliffe, James S; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C; Todorov, Alexandre A; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; Oord, Edwin J C G van den; Grootheest, Gerard Van; Os, Jim Van; Vicente, Astrid M; Vieland, Veronica J; Vincent, John B.; Visscher, Peter M; Walsh, Christopher A; Wassink, Thomas H; Watson, Stanley J; Weissman, Myrna M; Werge, Thomas; Wienker, Thomas F; Wijsman, Ellen M; Willemsen, Gonneke; Williams, Nigel; Willsey, A Jeremy; Witt, Stephanie H; Xu, Wei; Young, Allan H; Yu, Timothy W; Zammit, Stanley; Zandi, Peter P; Zhang, Peng; Zitman, Frans G; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R; Sklar, Pamela; Daly, Mark J; O'Donovan, Michael Conlon; Craddock, Nicholas John; Kendler, Kenneth S; Weiss, Lauren A; Wray, Naomi R; Zhao, Zhaoming; Geschwind, Daniel H; Sullivan, Patrick F; Smoller, Jordan W; Holmans, Peter Alan; Breen, Gerome.
In: Nature Neuroscience, Vol. 18, No. 2, 02.2015, p. 199-209.Research output: Contribution to journal › Article (Academic Journal) › peer-review
TY - JOUR
T1 - Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
AU - O'Dushlaine, Colm
AU - Rossin, Lizzy
AU - Lee, Phil H
AU - Duncan, Laramie
AU - Parikshak, Neelroop N
AU - Newhouse, Stephen
AU - Ripke, Stephan
AU - Neale, Benjamin M
AU - Purcell, Shaun M
AU - Posthuma, Danielle
AU - Nurnberger, John I
AU - Lee, S Hong
AU - Faraone, Stephen V
AU - Perlis, Roy H
AU - Mowry, Bryan J
AU - Thapar, Anita
AU - Goddard, Michael E
AU - Witte, John S
AU - Absher, Devin
AU - Agartz, Ingrid
AU - Akil, Huda
AU - Amin, Farooq
AU - Andreassen, Ole A
AU - Anjorin, Adebayo
AU - Anney, Richard
AU - Anttila, Verneri
AU - Arking, Dan E
AU - Asherson, Philip
AU - Azevedo, Maria H
AU - Backlund, Lena
AU - Badner, Judith A
AU - Bailey, Anthony J
AU - Banaschewski, Tobias
AU - Barchas, Jack D
AU - Barnes, Michael R
AU - Barrett, Thomas B.
AU - Bass, Nicholas
AU - Battaglia, Agatino
AU - Bauer, Michael
AU - Bayés, Mònica
AU - Bellivier, Frank
AU - Bergen, Sarah E
AU - Berrettini, Wade
AU - Betancur, Catalina
AU - Bettecken, Thomas
AU - Biederman, Joseph
AU - Binder, Elisabeth B
AU - Black, Donald W
AU - Blackwood, Douglas H R
AU - Bloss, Cinnamon S
AU - Boehnke, Michael
AU - Boomsma, Dorret I
AU - Breuer, René
AU - Bruggeman, Richard
AU - Cormican, Paul
AU - Buccola, Nancy G
AU - Buitelaar, Jan K
AU - Bunney, William E
AU - Buxbaum, Joseph D
AU - Byerley, William F
AU - Byrne, Enda M
AU - Caesar, Sian
AU - Cahn, Wiepke
AU - Cantor, Rita M
AU - Casas, Miguel
AU - Chakravarti, Aravinda
AU - Chambert, Kimberly
AU - Choudhury, Khalid
AU - Cichon, Sven
AU - Mattheisen, Manuel
AU - Cloninger, C Robert
AU - Collier, David A
AU - Cook, Edwin H
AU - Coon, Hilary
AU - Cormand, Bru
AU - Corvin, Aiden
AU - Coryell, William H
AU - Craig, David W
AU - Craig, Ian W
AU - Crosbie, Jennifer
AU - Cuccaro, Michael L
AU - Curtis, David
AU - Czamara, Darina
AU - Datta, Susmita
AU - Dawson, Geraldine
AU - Day, Richard
AU - Geus, Eco J De
AU - Degenhardt, Franziska
AU - Djurovic, Srdjan
AU - Donohoe, Gary J
AU - Doyle, Alysa E
AU - Duan, Jubao
AU - Dudbridge, Frank
AU - Duketis, Eftichia
AU - Ebstein, Richard P
AU - Edenberg, Howard J
AU - Elia, Josephine
AU - Ennis, Sean
AU - Etain, Bruno
AU - Fanous, Ayman
AU - Farmer, Anne E
AU - Ferrier, I Nicol
AU - Flickinger, Matthew
AU - Fombonne, Eric
AU - Foroud, Tatiana
AU - Frank, Josef
AU - Franke, Barbara
AU - Freedman, Robert
AU - Freimer, Nelson B
AU - Freitag, Christine M
AU - Friedl, Marion
AU - Frisén, Louise
AU - Gallagher, Louise
AU - Gejman, Pablo V
AU - Georgieva, Lyudmila
AU - Gershon, Elliot S
AU - Giegling, Ina
AU - Gill, Michael
AU - Gordon, Scott D
AU - Gordon-Smith, Katherine
AU - Green, Elaine K
AU - Greenwood, Tiffany A
AU - Grice, Dorothy E
AU - Gross, Magdalena
AU - Grozeva, Detelina
AU - Guan, Weihua
AU - Gurling, Hugh
AU - Haan, Lieuwe De
AU - Haines, Jonathan L
AU - Hakonarson, Hakon
AU - Hallmayer, Joachim
AU - Hamilton, Steven P
AU - Hamshere, Marian Lindsay
AU - Hansen, Thomas F
AU - Hartmann, Annette M
AU - Hautzinger, Martin
AU - Heath, Andrew C
AU - Henders, Anjali K
AU - Herms, Stefan
AU - Hickie, Ian B
AU - Hipolito, Maria
AU - Hoefels, Susanne
AU - Holsboer, Florian
AU - Hoogendijk, Witte J
AU - Hottenga, Jouke-Jan
AU - Hultman, Christina M
AU - Hus, Vanessa
AU - Ingason, Andrés
AU - Ising, Marcus
AU - Jamain, Stéphane
AU - Jones, Edward G.
AU - Jones, Ian R
AU - Jones, Lisa
AU - Tzeng, Jung-Ying
AU - Kähler, Anna K
AU - Kahn, René S
AU - Kandaswamy, Radhika
AU - Keller, Matthew C
AU - Kennedy, James L
AU - Kenny, Elaine
AU - Kent, Lindsey
AU - Kim, Yunjung
AU - Kirov, George
AU - Klauck, Sabine M
AU - Klei, Lambertus
AU - Knowles, James A.
AU - Kohli, Martin A
AU - Koller, Daniel L
AU - Konte, Bettina
AU - Korszun, Ania
AU - Krabbendam, Lydia
AU - Krasucki, Robert
AU - Kuntsi, Jonna
AU - Kwan, Phoenix
AU - Landén, Mikael
AU - Längström, Niklas
AU - Lathrop, Mark
AU - Lawrence, Jacob
AU - Lawson, William B
AU - Leboyer, Marion
AU - Ledbetter, David H
AU - Lencz, Todd
AU - Lesch, Klaus-Peter
AU - Levinson, Douglas F
AU - Lewis, Cathryn M
AU - Li, Jun
AU - Lichtenstein, Paul
AU - Lieberman, Jeffrey A
AU - Lin, Dan-Yu
AU - Linszen, Don H
AU - Liu, Chunyu
AU - Lohoff, Falk W
AU - Loo, Sandra K
AU - Lord, Catherine
AU - Lowe, Jennifer K
AU - Lucae, Susanne
AU - MacIntyre, Donald J
AU - Madden, Pamela A F
AU - Maestrini, Elena
AU - Magnusson, Patrik K E
AU - Mahon, Pamela B
AU - Maier, Wolfgang
AU - Malhotra, Anil K
AU - Mane, Shrikant M
AU - Martin, Christa L
AU - Martin, Nicholas G
AU - Matthews, Keith
AU - Mattingsdal, Morten
AU - McCarroll, Steven A
AU - McGhee, Kevin A
AU - McGough, James J
AU - McGrath, Patrick J
AU - McGuffin, Peter
AU - McInnis, Melvin G
AU - McIntosh, Andrew
AU - McKinney, Rebecca
AU - McLean, Alan W
AU - McMahon, Francis J
AU - McMahon, William M
AU - McQuillin, Andrew
AU - Medeiros, Helena
AU - Medland, Sarah E
AU - Meier, Sandra
AU - Melle, Ingrid
AU - Meng, Fan
AU - Meyer, Jobst
AU - Middeldorp, Christel M
AU - Middleton, Lefkos
AU - Milanova, Vihra
AU - Miranda, Ana
AU - Monaco, Anthony P
AU - Montgomery, Grant W
AU - Moran, Jennifer L
AU - Moreno-De-Luca, Daniel
AU - Morken, Gunnar
AU - Morris, Derek W
AU - Morrow, Eric M
AU - Escott-Price, Valentina
AU - Muglia, Pierandrea
AU - Mühleisen, Thomas W
AU - Muir, Walter J
AU - Müller-Myhsok, Bertram
AU - Murtha, Michael
AU - Myers, Richard M
AU - Myin-Germeys, Inez
AU - Neale, Michael C
AU - Nelson, Stan F
AU - Nievergelt, Caroline M
AU - Nikolov, Ivan
AU - Nimgaonkar, Vishwajit
AU - Nolen, Willem A
AU - Nöthen, Markus M
AU - Nwulia, Evaristus A
AU - Nyholt, Dale R
AU - Oades, Robert D
AU - Olincy, Ann
AU - Oliveira, Guiomar
AU - Olsen, Line
AU - Ophoff, Roel A
AU - Osby, Urban
AU - Owen, Michael John
AU - Palotie, Aarno
AU - Parr, Jeremy R.
AU - Paterson, Andrew D.
AU - Pato, Carlos N
AU - Pato, Michele T
AU - Penninx, Brenda W
AU - Pergadia, Michele L
AU - Pericak-Vance, Margaret A
AU - Pickard, Benjamin S
AU - Pimm, Jonathan
AU - Piven, Joseph
AU - Potash, James B
AU - Poustka, Fritz
AU - Propping, Peter
AU - Puri, Vinay
AU - Quested, Digby J
AU - Quinn, Emma M
AU - Ramos-Quiroga, Josep Antoni
AU - Rasmussen, Henrik B
AU - Raychaudhuri, Soumya
AU - Rehnström, Karola
AU - Reif, Andreas
AU - Ribasés, Marta
AU - Rice, John P
AU - Rietschel, Marcella
AU - Roeder, Kathryn
AU - Roeyers, Herbert
AU - Rothenberger, Aribert
AU - Rouleau, Guy
AU - Ruderfer, Douglas
AU - Rujescu, Dan
AU - Sanders, Alan R
AU - Sanders, Stephan J
AU - Santangelo, Susan L
AU - Sergeant, Joseph A
AU - Schachar, Russell
AU - Schalling, Martin
AU - Schatzberg, Alan F
AU - Scheftner, William A
AU - Schellenberg, Gerard D
AU - Scherer, Stephen W
AU - Schork, Nicholas J
AU - Schulze, Thomas G
AU - Schumacher, Johannes
AU - Schwarz, Markus
AU - Scolnick, Edward
AU - Scott, Laura J
AU - Shi, Jianxin
AU - Shilling, Paul D
AU - Shyn, Stanley I
AU - Silverman, Jeremy M
AU - Slager, Susan L
AU - Smalley, Susan L
AU - Smit, Johannes H
AU - Smith, Erin N
AU - Sonuga-Barke, Edmund J S
AU - Clair, David St.
AU - State, Matthew
AU - Steffens, Michael
AU - Steinhausen, Hans-Christoph
AU - Strauss, John S
AU - Strohmaier, Jana
AU - Stroup, T Scott
AU - Sutcliffe, James S
AU - Szatmari, Peter
AU - Szelinger, Szabocls
AU - Thirumalai, Srinivasa
AU - Thompson, Robert C
AU - Todorov, Alexandre A
AU - Tozzi, Federica
AU - Treutlein, Jens
AU - Uhr, Manfred
AU - Oord, Edwin J C G van den
AU - Grootheest, Gerard Van
AU - Os, Jim Van
AU - Vicente, Astrid M
AU - Vieland, Veronica J
AU - Vincent, John B.
AU - Visscher, Peter M
AU - Walsh, Christopher A
AU - Wassink, Thomas H
AU - Watson, Stanley J
AU - Weissman, Myrna M
AU - Werge, Thomas
AU - Wienker, Thomas F
AU - Wijsman, Ellen M
AU - Willemsen, Gonneke
AU - Williams, Nigel
AU - Willsey, A Jeremy
AU - Witt, Stephanie H
AU - Xu, Wei
AU - Young, Allan H
AU - Yu, Timothy W
AU - Zammit, Stanley
AU - Zandi, Peter P
AU - Zhang, Peng
AU - Zitman, Frans G
AU - Zöllner, Sebastian
AU - Devlin, Bernie
AU - Kelsoe, John R
AU - Sklar, Pamela
AU - Daly, Mark J
AU - O'Donovan, Michael Conlon
AU - Craddock, Nicholas John
AU - Kendler, Kenneth S
AU - Weiss, Lauren A
AU - Wray, Naomi R
AU - Zhao, Zhaoming
AU - Geschwind, Daniel H
AU - Sullivan, Patrick F
AU - Smoller, Jordan W
AU - Holmans, Peter Alan
AU - Breen, Gerome
PY - 2015/2
Y1 - 2015/2
N2 - Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
AB - Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
U2 - 10.1038/nn.3922
DO - 10.1038/nn.3922
M3 - Article (Academic Journal)
C2 - 25599223
VL - 18
SP - 199
EP - 209
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 2
ER -