Connection, compassion, and the genome

Evolution, the moral philosopher?

Steve W. Cole, Ph.D.

Social isolation

Inflammation
131

78

Lonely
Integrated

Immunoglobulin G1 production
Type I interferon antiviral response

Cole et al., Genome Biology, 2007

Low SES
Social loss / anticipated bereavement
Post-traumatic stress
Cancer diagnosis
Social threat
Loneliness
Social instability
Chronic stress
Low social rank
Caregiving for seriously ill
Depression
Early life low SES

Cole et al., Proc National Acad Sci USA, 2011

Irwin & Cole, Nature Reviews Immunology, 2011

How not to live

Lonely
Integrated

Irwin & Cole, Nature Reviews Immunology, 2011

How should we live?

What is the nature of true happiness?

Hedonic

Eudaimonic

How often do you feel happy?

How often do you feel satisfied?
Short Flourishing Hedonic
Life has direction and meaning?
Grow and become a better person?
Short Flourishing Eudaimonic
How often do you feel sad?
How often do you feel depressed?
CES-D

Eudaimonic-3
-2

-1

CESD

Hedonic

GBP1
IFI16
IFI27
IFI27L1
IFI27L2
IFI30
IFI35
IFI44
IFI44L
IFI6
IFIH1
IFIT1
IFIT1L
IFIT2
IFIT3
IFIT5

IFITM1
IFITM2
IFITM3
IFITM4P
IFITM5
IFNB1
IRF8
IRF2
IRF7
MX1
MX2
OAS1
OAS2
OAS3
OASL

IGJ
IGLL1
IGLL3
CD19

Eudaimonic

IL1A
IL1B
IL6
IL8
TNF
PTGS1
PTGS2

Hedonic

Eudaimonic

Hedonic

Eudaimonic

Hedonic

What is good?

What is bad?

Collaborators
Barb Fredrickson & PEP Lab
John Cacioppo, Louise Hawkley, Bob Rose
Steve Suomi, Jim Heckman, Gabriella Conti
Greg Miller, Edith Chen
Susan Lutgendorf, Anil Sood
John Sheridan, Nicole Powell
John Capitanio, Erica Sloan
Mike Irwin, Patti Ganz, Julie Bower
Margaret Kemeny, Jerry Zack
Teresa Seeman, Andrew Fuligni

Support
HopeLab Foundation
NCI CA116778, CA110793, CA109298
NIAID AI33259, AI36554, AI49135, AI52737
NIA AG107265, AG033590, AG34679
NIMH MH00820, MH15750
NCRR RR020645
NINR NR012899
MacArthur Foundation
James Pendleton Charitable Trust
Santa Fe Institute for Complex Systems
Norman Cousins Center

Social instability

CTRA conserved transcriptional response to adversity

Inflammation

Peer reared

MR.31
MR.44
MR.43
MR.41
MR.55
PR.47
PR.40
PR.37
PR.35

Mother reared

717
521

-----LOC712338
---EGR2
---FCER1A
LOC702878
LOC708902
LOC695437 /// LOC705266
ARL4C
---PF4
-----LOC711141
WIF1
--------CPA3
LOC711501
LOC699196
POLR1C
LOC722567
---LOC695437
LOC702846
/// LOC705266
---LOC715357
---LOC700750
---LOC702775
LOC703781
LOC695193
LOC704412
---LOC715511
---LOC701889
LOC709901
---LOC709540
---LOC712403
---LOC698275
LOC714786
LOC693850
HMGCS2
---LOC711302
LOC715974
---LOC711141
---LOC705093
LOC711501
LOC719284
---LOC706836
LOC702153
------HIPK2
LOC706531
POLR1C
LOC712754
LOC708226
LOC699418
LOC703567
LOC701218
LOC711386
------LOC699255
---CEP290
---LOC696021
PDE7A
ITGA6
---LOC713460
NDFIP2
LOC695780
ZC3H13
------LOC716013
LOC696063
FOS
SFRS5
FZD10
LOC706873
C16orf70
DYRK2
---PDE6A
---LOC700615
---LOC702307
LOC718408
---GPR183
---LOC708930
LOC695437
---LOC710080
---ZNF397
LOC704667
LOC698904
---LOC710319
---LOC711787
LOC696756
---LOC698329
LOC710361
LOC707743
---MGST1
---LOC717228
LOC696407
LOC693803
---LOC707560
---LOC716949
LOC708094
---LOC710744
---LOC715357
LOC716475
LOC717288
LOC700747
---LOC693428
---LOC702705
LOC715683
LOC704916
MYC
IL8
------ITGA6
LOC703018
------LOC701038
PRMT6
LOC708226
LOC712125
LOC705551
AXIN2
LOC715015
CYTH1
LOC700843
LOC714223
LOC703152
SLC27A2
---ME2
---LOC705946
LOC703326
CTGF
LOC704916
LOC702516
LOC710276
LOC698785
LOC718091
---LOC707388
------CD8B
LOC704412
LOC711063
---RAB11FIP2
---LOC701837
LOC707195
LOC697577
------LOC702158
LOC712079
LOC712825
KLF4
------LOC705093
LOC698337
---LOC704037
-----LOC717288
---LOC705228
LOC697813
---LOC713831
LOC704248
---EXPH5
---LOC716408
LOC695429
LOC699511
---ZXDB
LOC701919
LOC693270
LOC702385
---CD5L
LOC694817
------LOC703456
------CSPG5
LOC697206
---LOC704412
LOC694723 /// LOC718160
LOC706456
---LOC703458
LOC710951
---LOC694159
PTTG1
---LOC704221
LOC710290
LOC715526
LOC704362
---LOC713436
SUCLA2
LOC698632
---LOC717824
LOC697718
---LOC712568
LOC705491
LOC721394
IGKV1-5 /// LOC720225
---CAMK4
LOC710457
------LOC706229
LOC708691
ZNF141
LOC717589
LOC715927
LOC717280
---LOC721789
------LOC696086
RCHY1
---LOC704292
---LOC701555
---LOC700118
LOC714761
------KIAA0562
ZXDB
---MGST1
---LOC701522
---SLC26A2
LOC702135
LOC696416
---ZNF226
LOC709585
LOC708812
ADD3
---LOC717092
LOC715927
---LOC697740
LOC710690
LOC704513
---LOC700222
LOC712125
LOC696606
------LOC722528
LOC704624
---LOC694961
LOC694190
---LOC703373
ITPR1
---LOC712825
---LOC710942
LOC709483
---DYRK2
------LOC705788
LOC722004
H1F0
---LOC695606
LOC698759
LOC711066
---LOC710966
LOC711280
---LOC700869
LOC696006
LOC711975
---LOC701669
LOC695399
EXOSC3
---LOC704451
---ATP1B1
LOC711071
---LIMA1
XCL1
LOC708871 /// LOC709304
------LOC707664
SMC3
---LOC714764
---LOC715471
------LOC695606
LOC705346
---ZNF146
ZMYND11
LOC705611
LOC704301
CAMK4
---LOC697095
LOC708808
SATB1
LOC703458
DDX20
LOC705480
LOC709960
---LOC704695
LOC722935
---LEO1
---LOC697232
LOC694351
LOC695453
---LOC699511
---LOC696416
---GSTT1
LOC710966
LOC702550
SENP7
LOC694500
---LOC718554
FN1
LOC696091
LOC696004
CDC37
LOC693663
---LOC694909
LOC703693
LOC693565
LOC700709
LOC705480
---ZC3H13
PDE7A
LOC713463
BXDC2
LOC699509
LOC695153
TRB@
---LOC697319
LOC708734
---CCR7
---LOC705946
---LOC706873
RPS6KB1
LOC714480
LOC701340
LOC703367 /// ZDHHC4
XG
CGB8
BIRC3
ITGA6
LOC706563
---TTC3
---DLD
LOC694298
LOC717518
LOC722107
LOC714761
---ARL4C
---MKI67IP
---LOC709656
DOCK10
LOC716820
---LOC704667
---RBL2
------LOC720204
LOC695147
LOC700198
PIGK
---LOC700708
---LOC713236
LOC694043
GPAM
---LOC704154
---RWDD3
---LOC702568
SAR1A
---LOC694760
---LOC709008
ZNF195
---TNFAIP3
SEC24A
LOC696756
---LOC714059
LOC706541
LOC710580
LOC713415
LOC717294
---LOC696945
EXOC5
LOC695826
---ATF1
---LOC696131
RCHY1
---LOC696756
BCOR
LOC696883
---LOC706314
TBC1D19
RHOBTB1
---LOC700505
LOC710176
TRB@
LOC716408
---LOC695544
LOC714008
GPAM
LOC719983
LOC716755
---LOC715437
---ZYG11B
PROSC
LOC721420
---LOC717679
LOC717473
---LOC707119
SATB1
---GNE
LOC710951
LOC701890
TIMM17A
ADSS
LOC698247
LOC707992
ZC3H13
LOC715660
LOC713173
---PLEKHG1
LOC709962
LOC718651
------LOC710611
LOC706456
LOC709702
LOC701837
---LOC703452
LOC695224
PB1
---MAP1B
---LOC697490
LOC696772
BIRC3
------LOC708226
LOC696961
---LOC715410
GSTA1
LOC710951
---CAPN2
GYPA
---ADD3
---RCHY1
LOC704367
LYZ
---LOC698974
LOC707873
---LOC715074
---LOC693281
---TMPO
LOC698329
LOC716189
---NAALAD2
---LOC712712
---MED6
LOC707390
RAB11FIP2
MSH2
LOC697652
LOC654415
---LOC700365
------CMAS
LOC711940
LOC695219
---LOC717492
---LOC700074
LOC698247
---LOC700476
LOC713453
CMAS
EIF2S1
---LOC713436
SLC7A11
LOC698683
---LOC697235
---LOC720016
SHC2
LOC718868
LOC719127
LOC715767
LOC710986
LOC709790
LOC693759
DUSP5
---LOC715967
PSG2
LOC698947
---LOC713630
------IL15
LOC698953
NCF1
LOC719260
LOC712282
LOC711784
LOC703083
RALB
LOC699977
LOC707395
---MSRA
LOC701759
LOC704667
LOC712342
LOC721106
LOC710909
LOC703901
------RRP22
---LOC698917
---LOC713191
FGR
LOC698953
SAT1
---PTAFR
---LOC574145
TLR4
---GADD45A
LOC717038
SYK
---LTB4R
FFAR2
LOC712466
LOC719301
---CLEC7A
LOC698683
------RXRA
GOT2
---WARS
LOC696060
---TBX21
FPR2
LOC706642
---MDM2
---LOC719595
LOC707336
---SGSH
---LOC707033
LOC701759
KIR2DL4
GADD45B
/// KIR3DH5
---LOC719412
---LOC717811
LOC708852
TLR6
LOC703028
LOC714931
---LOC701101
LOC710864
---CTBP2 /// LOC705737
---LOC706221
CTSD
GPR153
---LOC710986
------LOC708948
LOC695092
LOC702406
---LOC703777
---LOC694684
GPR87
LOC704355
TNFSF13B
TNFRSF1B
LOC711079
LOC710384
LOC715071
DGKG
LOC707383
---LOC715516
---MDM2
LOC697857
---LOC722311
---LOC696345
LOC705865
LOC708602
LOC710650
LOC700215
GADD45B
---LOC711746
LOC703083
---LOC695734
SIGLEC5
---LOC717799
IDO1
LOC699236
LPL
LOC705700
ATP5B
---LOC711743
---LOC693660
LOC574145
APBB2
LOC712466
NCF1
LOC715767
LOC721138
LOC712342
LOC694240
LOC722564
---PLA2G7
LOC711303
---LOC697977
---LOC574146
LOC708852
LOC696549
LOC705061
SLC31A2
DAPP1
LOC696050
---LOC719654
LOC711746
LOC699497
---LOC694225
CYP3A5
---LOC711743
NCF1
LOC718993
GK
---LOC698947
---TLR4
LOC709760
LOC707687
---LOC574145
---LOC714584
LOC715924
DDX58
CCL5
---AOAH
HMGCL
---EFHD2
KLRC3
GADD45B
LOC696549
LOC712358
---NOTCH4
KLRC3
UPP1
LRP2
------LOC693532
KLHL2
ITGA2B
LOC710375
KLRC3
ANXA3
LOC701234
---UPP1
APBB2
LOC713191
LOC694871
------IGHG1 /// LOC711303
LOC695612
---LOC719654
---CYTH4
---LOC700632
IFITM3
---LOC711743
LOC698947
LILRAB
LOC710267
LOC701826
LY96
CD14
LOC722305
BIK
LOC701759
LOC716161
KIR3DL12
LOC710216
LOC716161
KLRF1
LOC704216
-----LOC714968
---GSN
FES
FOSL2
COL15A1
WARS
LOC705554
LOC697835
LOC693532
------PRDM1
DDIT4
---LOC717799
SLC11A1
LOC711743
---LOC697718
TREM1
---LOC695612
---LOC694684
LOC696824 /// LOC703106 /// LOC703892 /// LOC713723 /// LOC719483 /// LOC719702 /// LOC720309 /// LOC720330 /// LOC720342 /// LOC720369 /// LOC720696 /// LOC723284 /// LOC723473 /// MAMU-A /// MAMU-B /// MAMU-B18 /// MAMU-I
---LOC694502
LRP2
LOC712046
---LOC706221
LILRBC
LOC716978
GBP1
LOC705670
LOC705568
---LOC697656
IGKV1-5
GLUL
LOC718307
LOC712977
LOC695158
------LOC694225
LOC722774
---SERPINA1
---LOC716337
LOC708383
---LILRA2
/// LILRAB /// LILRAC /// LOC722780
F2RL1
LOC710706
LOC694699
---LOC711291
LOC693954
LOC695612
LTB4R
LOC693768
POLR1D
------SLC11A1
LOC694871
---LOC700993
SLC11A1
C1QA
LOC693567
IL15
---MAMU-DQB1
---LOC693954
LOC697235
MX2
LOC707236
LOC704994
LOC700486
SERPINA1
IRAK3
LOC717218
TKTL1
LOC695560
SP100
LOC700653
CLIC5
LOC722305
LOC695323
IL15
---LOC717665
LOC714427
---DYSF
LOC701433
---LOC697235
LOC713485
LOC708852
LOC722130
---MX2
---LOC695437 /// LOC705266
---LOC710350
NKG7
LOC694225
LILRBC
ST3GAL4
LOC705298
LOC710740
---LOC693838
CD82
---LOC694699
---LOC702540
LOC704850
---MAMU-A
------IFI27
---IFITM3
LOC716043
--------LOC713232
LOC707359
LOC705096
IRF7
LOC694847
------TLR5
GBP1
LOC713232
LOC707116
BDKRB2
LOC714584
------LOC710518
GZMB
---MAMU-DQB1
LOC710518
LOC574146
---LOC574122
---GBP1
LOC720006
------GBP1
LOC705416
LOC710740
CYP3A5
LOC700141
---GBP1
LOC710518
---LOC693427
LOC712753
LOC702540
LOC695344
---LOC696808
---LOC698943
LOC713715
---MNP1A
---MX1
LOC708344
IFITM3
LOC695344
LOC700208
IFIT2
LOC702381
LOC693768
GBP1
------LOC697200
LOC695344
IFIT2
LOC715108
LOC722730
---LOC719654
---LOC720683
LOC707854
LOC707854
LOC719243
AMBP
--IFIT1

Immunoglobulin G1 production
Type I interferon antiviral response

Irwin & Cole, Nature Reviews Immunology, 2011

Cole et al., Proc National Acad Sci USA, 2011

Irwin & Cole, Nature Reviews Immunology, 2011

Irwin & Cole, Nature Reviews Immunology, 2011