13/11/2019 COPE WEBINAR SERIES FOR HEALTH PROFESSIONALS November - - PDF document

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COPE WEBINAR SERIES FOR HEALTH PROFESSIONALS November 13, 2019 Using g e ne tic informa tion to pre dic t a nd tre a t obe sity: Ar e we r e ady for pr e c ision me dic ine ?

Moderator: Lisa Diewald, MS, RD, LDN Program Manager MacDonald Center for Obesity Prevention and Education

• M. Louise Fitzpatrick College of Nursing

Nursing Education Continuing Education Programming Research

FINDING SLIDES FOR TODAY’S WEBINAR www.villanova.edu/COPE Click on Loos webinar description page

Nursing Education Continuing Education Programming Research

DID YOU USE YOUR PHONE TO ACCESS THE WEBINAR?

If you are calling in today rather than using your computer to log on, and need CE credit, please email cope@villanova.edu and provide your name so we can send your certificate.

Nursing Education Continuing Education Programming Research

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OBJECTIVES

Nursing Education Continuing Education Programming Research

• Discuss genetic testing directly-to-consumers (DTC)

services, advertised as providing genetically matched diets based on genotype data.

• Explain the basic principles of prediction and the

limitations of using genetic information in personalizing diet and exercise prescriptions.

• Identify other opportunities for personalizing health

related behaviors. CE DETAILS

Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center Commission on Accreditation Villanova University College of Nursing Continuing Education/COPE is a Continuing Professional Education (CPE) Accredited Provider with the Commission on Dietetic Registration

Nursing Education Continuing Education Programming Research

NUTRITION FUTURE FORWARD: ARE WE READY FOR OUT OF THE BOX THINKING?

March 6, 2020 9 AM-4 PM Driscoll Hall Auditorium Villanova University RNs: 6 contact hours RD/ RDN/ DTR: 6 CPEUs

Villanova.edu/cope

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CE CREDITS

• This webinar awards 1 contact hour for nurses

and 1 CPEU for dietitians

• Suggested CDR Learning Need Codes: 2000,

2050, 5370, and 9020

• Level 2
• CDR Performance Indicators: 6.2.5, 8.3.6, 8.3.7

Nursing Education Continuing Education Programming Research

Using genetic information to predict and treat

• besity: Are we ready for precision medicine?

Ruth Loos, PhD. Charles Bronfman Professor in Personalized Medicine Icahn School of Medicine Wednesday, November 13, 2019 12-1 PM EST DISCLOSURE The planners and presenter of this program have no conflicts of interest to disclose. Accredited status does not imply endorsement by Villanova University, COPE or the American Nurses Credentialing Center

• f any commercial products or medical/nutrition advice

displayed in conjunction with an activity.

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Using g e ne tic informa tion to pre dic t a nd tre a t obe sity:

Ar e we r e ady for pr e c ision me dic ine ?

Ruth L

• os

Charle s Bro nfman Pro fe sso r in Pe rso nalize d Me dic ine Cha rle s Bro nfma n Institute fo r Pe rso na lize d Me dic ine Mindic h Child He a lth a nd De ve lo pme nt Institute Ic a hn Sc ho o l o f Me dic ine a t Mo unt Sina i Ne w Yo rk ruth.lo o s@ mssm.e du Vi l l anova COPE Webi nar , November 13t h 2019 NCD Risk F ac to r Co llab o ratio n L anc e t 2017

Ove rwe ig ht/ obe sity pre va le nc e in USA sinc e 1980’s Girls Wo me n Bo ys Me n Obe sity “runs” in fa milie s

Ca na da F itne ss Surve y N = 15,245, a g e d 7 – 69 yrs, fro m 6,377 fa milie s Katzmarzyk e t al. AJE , 1999

Ge ne s Sha re d e nviro nme nt Sha re d e nviro nme nt

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Both g e ne s a nd e nvironme nt c ontribute to obe sity risk

Bo rje so n Ac ta Pae d Sc and 1976

DZ MZ

T win studie s F amily studie s

h2 = 40- 70%

Obe sity is he rita ble , more tha n 1,000 loc i ha ve be e n ide ntifie d

200 400 600 800 1000 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Cumulative number of loci identified Childhood Obesity and BMI Extreme and early onset Obesity Overweight and obesity BMI (African) BMI (Asian) BMI (predominantly European)

Why study g e ne tic s of obe sity ?

Speliotes et al. Nature Genetics 2010 Siljee et al. Nature Genetics 2018 Khera et al. Nature Genetics 2018

Ge ne - disc ove ry Biolog y & me c ha nisms Pre dic tion & Dia g nostic s

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Using g e ne tic informa tion throug hout the life -c ourse

Dia g nose & tre a t dise a se Pre dic t & pre ve nt dise a se

Pre c ision me dic ine to tre a t obe sity, ma inta in he a lthy we ig ht

Pr e c ision me dic ine a nd c ommon obe sity

Common obe sity

• Many ge ne tic var

iants in many g e ne s tha t a c t thro ug h multiple pathways tha t ha ve small e ffe c ts.

• L

ife style a nd e nviro nme nt a re impo rta nt.

• He rita b ility 40-70%
• One

mutation in o ne g e ne tha t affe c ts a spe c ific pathway a nd ha ve a lar ge e ffe c t.

• L

ife style a nd e nviro nme nt ha ve mino re ffe c t.

Monoge nic for ms of obe sity

F a ro o q i e t a l. NE JM 1999 L E P L E PR Sa e e d e t a l. Ob e sity 2014 F a ro o q i e t a l. NE JM 2003 MC4R POMC K rud e e t a l. Na t Ge n 1998

 L E P muta tions  Re c ombinant human le ptin  muta tions in POMC, L E PR

,…  MC4R a g onists

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Sc re e ning

• E

xpo so me (life style , e nviro nme nt)

• Ge no me
• T

ra nsc ripto me , … T re atme nt base d

• n profile

So urc e : MD Ande rso n L

• w satur

ate d fat die t Ae robic e xe rc ise High- fat die t L

• w glyc e mic die t

High fibe r die t

Pr e c ision me dic ine in the g e nome e r a – ta ilor e d tr e a tme nt

• ne e d to e a t me a t virtua lly

e ve ry da y to sa tisfy yo ur a nc ie nt hunte r-g a the re r g e ne s

• a vo id o a ts, whe a t, a nd mo st

g ra ins

• e vo lve d a fte r the sta rt o f

a g ra ria n so c ie ty

• b e st o ff a s ve g e ta ria n
• e me rg e d a s huma ns

mig ra te d to wa rd c o lde r c lima te s

• the mo st va rie d die t,

inc luding me a t

• do e s we ll with da iry

pro duc ts

• the b e ne fits a nd into le ra nc e s o f

type s A a nd B

T he Blood-T ype die t

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Dir e c t- to- c onsume r c ompa nie s ma ke bold c la ims

Ruth L

• o s

A c a se study – he a lthy woma n se e ks a dvic e

• 48 ye a r o ld wo ma n
• Ge ne ra lly he a lthy, physic a lly a c tive ,

he a lthy die t, do e s no t smo ke ,…

• Wa nts a dvic e fo r he a lthy a g ing

 DT C te st tha t inc lud e s te sts o n we llne ss A c a se study – the e vide nc e

F r amingha m Offspr ing Pue r to Ric a n Ce nte r s on PHHD study

• No da ta o n we ig ht g a in
• One va ria nt – wha t a b o ut o the r

va ria nts ?

• Wha t is the a dvic e fo r T
• a lle le

c a rrie rs ?

• Sig nific a nt inte ra c tio n <>

pre d ic tive

• No da ta o n we ig ht g a in
• One va ria nt – wha t a b o ut o the r

va ria nts ?

• Wha t is the a dvic e fo r T
• a lle le

c a rrie rs ?

• Sig nific a nt inte ra c tio n <>

pre d ic tive Pue r to Ric a n Ce nte r s on PHHD study

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A c a se study – the e vide nc e

• Ho w muc h “pre c isio n” do e s this

info rma tio n a dd in the c o nte xt o f pre c isio n me dic ine ?

• Ho w muc h “pre c isio n” do e s this

info rma tio n a dd in the c o nte xt o f pre c isio n me dic ine ?

• Sma ll (inte ra c tio n) e ffe c ts

 b ig g e r e ffe c ts that disc riminate b e twe e n g e no type s

• One SNP a t a time , o ne e xpo sure (d ie t, phys a c t, …) a t a time

“F ull pic ture ” (”b ig data”) is ne e de d

• F

e w studie s tha t e xa mine “c ha ng e ” in re spo nse to a n e xpo sure  L

• ng itudinal studie s o n we ig ht c hang e , inte rve ntio ns (L
• o k AHE

AD, DPP, POUNDS L OST , …) Cha lle ng e s for pre c ision me dic ine in c ommon obe sity

Pre c ision me dic ine to pre dic t obe sity

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SNPs – Sing le Nuc le otide Polymorphisms GGC GCC GGA CGC TCC ATC TCC TGG GCC TGG TGG GCA TGT GTG

Gly Ala Gly Arg Ser Ile Ser Trp Ala Trp Trp Ala Cys Val

GGC GCC GGA CGC TCC ATC TCC TGG GCC TGG TGG GCA TGT GTG GGC GCC GGA CGC ACC ATC TCC TGG GCC TGG TGG GCA TGT GTG GGC GCC GGA CGC TCC ATC TCC TGG GCC TGG TGG GCA TGT GTG GGC GCC GGA CGC TCC ATC TCC TGG GCC TGG TGG GCA TGT GTG GGC GCC GGA CGC TCC ATC TCC TGG GCC TGG TGG GCA TGT GTG GGC GCC GGA CGC ACC ATC TCC TGG GCC TGG TGG GCA TGT GTG GGC GCC GGA CGC ACC ATC TCC TGG GCC TGG TGG GCA TGT GTG GGC GCC GGA CGC TCC ATC TCC TGG GCC TGG TGG GCA TGT GTG GGC GCC GGA CGC ACC ATC TCC TGG GCC TGG TGG GCA TGT GTG A A A A T T T T T T

Gly Ala Gly Arg Thr Ile Ser Trp Ala Trp Trp Ala Cys Val

T/T A/T A/A T/T A/T

SNP  Single Nucleotide Polymorphism Polyg e nic risk sc ore s

One SNP- a ssoc ia tion

SNP 1 1 2 2 SNP 2 1 2 2 2 1 SNP 3 2 1 2 2 SNP 4 … SNP 5 … SNP 6 … SNP 7 … SNP 8 … PRS 7 8 4 12 7 8 25.2 26.6 27.9 24 25 26 27 28 29 T / T A/ T A/ A SNP - Ge notype BMI (kg / m 2)

1 2

SNP … … SNP … … So urc e : RGA

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Asse ssing pre dic tive va lue of a (g e ne tic ) te st

Se nsitivity o f te st

• % o f all ‘ o b e se ’ tha t we re c o rre c tly ide ntifie d

b y the te st

Spe c ific ity o f te st

• % o f all ‘ no n-o b e se ’ tha t we re c o rre c tly

ide ntifie d b y the te st

Dise ase

Obe se Not obe se

Pr e dic tion T e st

e .g. PRS, family histor y

Obe se T

• p de c ile PRS

Not obe se Othe r de c ile s PRS

T RUE + T RUE

• F

AL SE + F AL SE

• Se nsitivity

Spe c ific ity 0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1

1-specificity sensitivity

0.8 0.2 0.4 0.6 1

AUCnull = 0.50 AUCperfect = 1.00

F amily histor y Whita ke r e t al NEJM 1997

AUC > 0.80 25 26 27 28 29 Mean BMI (kg/ m 2) 500 1000 1500 Number of individuals (N) Number of weighted risk alleles

2 .7 3 kg/ m 2

7 .0 - 8 .8 5 kg

0.25 0.50 0.75 1.00 Sensitivity 0.25 0.50 0.75 1.00 1-Specificity AUC3 2 SNPs = 0 .5 7 4

F amily histor y

Pre dic ting obe sity with c ommon g e ne tic va ria nts

Speliotes et al Nature Genetics 2010

Pre dic ting obe sity with c ommon g e ne tic va ria nts

Ye a r SNPs E xpla ine d va r ia nc e in BMI ROC AUC 2007 F ra yling e t a l. F T O 0.34 % 0.546 2008 L

• o s e t a l.

F T O+MC4R 0.55 % 0.55 2009 Wille r e t a l. 12 SNPs 0.90 % 0.574 2010 Spe lio te s e t a l. 32 SNPs 1.5% 0.574 2015 L

• c ke e t a l.

97 SNPs 2.7 % 0.601* 2019 Khe ra e t a l. 2.1M SNPs 8.5 % ?

0.636 AUC 32SNPs = 0.574 AUC 97SNPs = 0.601 AUC 2MNPs = 0.636

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288,016 individua ls o f the UK Bio b a nk

Pre dic ting obe sity with c ommon g e ne tic va ria nts

1.2% 51.6% 37.7% 9.2% 0.2% 0.4% 32.4% 43.8% 21.8% 1.5% 0.2% 17.0% 39.6% 37.6% 5.6% 0% 10% 20% 30% 40% 50% Unde r we ig ht Norma l Ove r we ig ht Obe se Se ve re ly obe se Bo tto m De c ile De c ile s 2-9 T

• p De c ile

346 14,862 10,858 2,650 58 922 74,654 100,921 50,230 3,456 58 4,896 11,405 10,829 1,613 20,000 40,000 60,000 80,000 100,000 Unde r we ig ht Norma l Ove r we ig ht Obe se Se ve re ly obe se Bo tto m De c ile De c ile s 2-9 T

• p De c ile

K he ra e t a l. Ce ll 2019 31% c o rre c tly ide ntifie d a s hig h risk 17% c o rre c tly ide ntifie d a s hig h risk

Pre dic ting obe sity e a rly in life for pre ve ntion

T

• rka ma ni & T
• po l Ce ll 2019

A c a se study – he a lthy woma n se e ks a dvic e

• 48 ye a r o ld wo ma n
• Ge ne ra lly he a lthy, physic a lly a c tive ,

he a lthy die t, do e s no t smo ke ,…

• Wa nts a dvic e fo r he a lthy a g ing

 DT C te st tha t inc lud e s te sts o n we llne ss

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Doe s knowing your g e ne tic risk a ffe c t your be ha vior ?

• Ge no me -wide pro filing with Na vig e nic s He a lth Co mpa ss to e stima te life time risk o f 23

dise a se s/ tra its

• 3,639 individua ls fro m he a lth a nd te c hno lo g y c o mpa nie s e nro lle d in study; 2,037 (56%)

c o mple te d fo llo w-up a t 3 mo nths a nd 1,325 (36%) c o mple te d fo llo w-up a t 1 ye a r

• Anxie ty sympto ms, die ta ry fa t inta ke , e xe rc ise b e ha vio ur

Would g e ne tic pre dic tion c ha ng e be ha vior ?

• Ove ra ll, no short- or long - te rm c ha ng e s in psyc ho lo g ic a l he a lth, die t o r e xe rc ise

b e ha vio r.

Blo ss e t al NE JM 2011 & JMG 2013 Ove r all life time r isk Obe sity life time r isk Shor t- te r m P= 0.74 P = 0.76 P=0.46 ‐0.03 0.03 0.06 0.09 Anxiety Dietary fat intake Exercise Change in behaviour/life me risk P= 0.35 P = 0.005 P=0.95 ‐0.03 0.03 0.06 0.09 Anxiety Dietary fat intake Exercise Change in behaviour/life me risk

Would g e ne tic pre dic tion c ha ng e be ha vior ?

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Ove r all life time r isk Obe sity life time r isk L

• ng - te r

m ‐0.03 0.03 0.06 0.09 Anxiety Dietary fat intake Exercise Change in behaviour/life me risk P= 0.90 P = 0.95 P=0.68 ‐0.03 0.03 0.06 0.09 Anxiety Dietary fat intake Exercise Change in behaviour/life me risk P= 0.31 P = 0.30 P=0.44

Would g e ne tic pre dic tion c ha ng e be ha vior ?

• Ove ra ll, no short- or long - te rm c ha ng e s in psyc ho lo g ic a l he a lth, die t o r e xe rc ise

b e ha vio r.

Blo ss e t al NE JM 2011 & JMG 2013

• T

he c urre nt c o ntrib utio n o f g e ne tic info rma tio n to pre c isio n me dic ine in o b e sity is limite d  o b e sity, we ig ht g a in, we ig ht lo ss a re c o mple x, multifa c to ria l a nd po lyg e nic tra its tha t c a nno t b e c a pture d b y a sing le g e ne tic sc o re .

• F

ull(e r) pic ture is ne e de d. Othe r, no n-g e ne tic fa c to rs, mig ht b e mo re info rma tive to pe rso na lize tre a tme nt a nd impro ve pre dic tio n.

• T
• ta ilo r tre a tme nts to pe o ple ’ s g e ne tic a nd no n-g e ne tic “pro file ”, we ne e d

mo re re se a rc h into the “pre dic to rs” o f re spo nse to a va rie ty o f tre a tme nts.

• L

ife style a nd b e ha vio r a re ha rd to c ha ng e – e ve n if pe o ple re c e ive “so phistic a te d” info rma tio n, it ma y still no t b e po ssib le to a d o p t ne w re c o mme nda tio ns.

Conc lusions

G ANT G ANT

C O N S O R T I U M

Colla bor a tor s a nd a c knowle dg e me nts

Misa Gra ff, Mic ha e l Pre uss, Sa o ri Sa ka ue , Io a nna Nta lla , So nja Be rndt, Sa ila ja Ve da nta m, Ada m E . L

• c ke , E

irini Ma ro uli, L

• ic Ye ng o , Anne Justic e , K

ristin Yo ung , Ying c ha ng L u, a nd ma ny mo re

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Prevention of ASCVD in South Asians: Impact of Diet Modification and Physical Activity as Primary Intervention Geeta Sikand, MA, RDN, FAND, CDE, CLS, FNLA Director of Nutrition University of California Irvine Prevention Cardiology Program Wednesday, November 13, 2019 12-1 PM EST QUESTIONS & ANSWERS

Moderator: Lisa K. Diewald MS, RD, LDN Email: cope@villanova.edu Website: www.villanova.edu/COPE

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