Table S6
TableS6.Pleiotropiclinksbetweenrandomlychosengenesandearly-life
fitness-relatedtraits.Fitness-relatedtraitsincludefertilitypotential,reproductive
outcomes,pregnancyoutcomes,fetalgrowthandsurvival,i.e.affectingtheabilityof
anorganismtoreproduceandtransfergenestothenextgeneration.Thefirst
columngivescoronaryarterydisease(CAD)gene(first20of40CADgenesfromFig.
1B/TableS1).Columns2-3givename(abbreviated,full)ofrandomlychosengenes
matchedforapproximatelengthforeachCADgene.Columns4-8providekeydetails
ofeachstudywhererandomgenesalsocontributetotraitsthatinfluencefitness,
includingwhatspeciesthatwasdemonstratedin,whatbiologicalprocessorfitness
effectsthatgeneisimpacting,whatfitnessclassthateffectislikelytoimpact(e.g.
dysfunctionalspermatogenesisorembryogenesiswillaffectmaleandfemale
fertility,abilitytoconceive),whattheobservedgeneticeffectormechanismthat
genewasassociatedwith.
CADgene Random fullname
Gene
BCAS3
STPG2 SpermTailPG-Rich
RepeatContaining2
CNNM2
CFAP44 CiliaAndFlagella
AssociatedProtein44
TEX41
SHISA9 ShisaFamilyMember
9
SMG6
TANGO6 TransportAndGolgi
Organization6
Homolog
PHACTR1 SUMF1 SulfataseModifying
Factor1
COG5
ABCG8
RAI1
NT5C2
LDLR
KCNK5
ABO
SWAP70
species fitnesseffects fitnessclass*
-
-
-
observedgeneticeffectorref
mechanism
-
-
-
-
-
-
-
-
-
-
-
-
-
mouse
embryogenesis femalepotential SUMF1significantlyupfertility
regulatedin
developmentally
incompetentmouse
oocytes
-
-
-
FRMD5 FERMDomain
-
Containing5
ASIC5 AcidSensingIon
-
ChannelSubunit
FamilyMember5
ZNF516 ZincFingerProtein
human
516
LANCL1- LANCL1Antisense
-
AS1
RNA1
SYT13 Synaptotagmin13
-
FAM53A FamilyWithSequence -
Similarity53Member
A
TTC22 Tetratricopeptide
-
RepeatDomain22
RNF157 RingFingerProtein cattle
157
RNF157
[1]
-
-
-
endometriosis
-
femalepotential ZNF516appearstobe
[2]
fertility
involvedinendometriosis
-
-
-
-
-
-
-
-
-
-
-
oocyte/follicle femalepotential Incattlemodel,RNF157
[3]
maturation
fertility
2.24significantly
(oocytequality)
differentiallyup-regulated
betweenBCB+andBCB-
oocytes
human earlyperipheral pregnancy
RNF157is-1.65fold
[4]
bloodgene
complications/ou significantly(P=0.01)
S31
Table S6
SH2B3
PLBD1- PLBD1AntisenseRNA -
AS1
1
PEMT
WAC
WWDomain
-
ContainingAdaptor
WithCoiled-Coil
MRAS
TMEM17 Transmembrane
-
8A
Protein178A
KIAA1462 PLEKHD PleckstrinHomology -
1
AndCoiled-Coil
DomainContainingD1
GUCY1A3 MACC1 MetastasisAssociated -
InColonCancer1
CDKN2B- CACNA2 CalciumVoltage-Gated -
AS1
D4
ChannelAuxiliary
SubunitAlpha2delta4
ANKS1A NWD2 NACHTAndWD
-
RepeatDomain
Containing2
expression
during
pregnancy
relatedto
preeclampsia
-
tcomes
down-regulatedin
peripheralblood
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Tablefootnotes:
*'fitnessclass'columndefinedfurther:
malepotentialfertility
-
includesprocessesaffectingspermatogenesis,spermmotility,volumeor
functionthatultimatelyaffectprobabilityofsuccessfuleggfertilization.
femalepotentialfertility -
includesprocessesaffectingembryogenesis(i.e.oocyteviability,survival),
functioningofuterus(i.e.implantationreceptivity,endometriumfunctioning),
placentation(trophoblastcellmotility)thatultimatelyaffectsinitialsuccessful
establishmentofpregnancy.
pregnancyoutcomes
-
includesprocessesaffectingregulationofbloodpressure,nutrientandoxygen
transferbetweenfetalandplacentaltissuesduringpregnancythatultimately
influencesfetalgrowth,developmentandsurvival.
fetal/offspringmortality -
includesprocesseslinkedtopregnancydefects,resistancetopathogens,
affectingsurvivaloffetusduringpregnancyorperinatalmortality.
reproductiveoutcomes
-
includeseffectsonageatmaturity,reproductivetiming,potentialnumberof
offspring,breastfeedingcapacity.
Searchcriteria:
•
Foreachrandomgene,Googlescholarwasusedtosearchforstudiesusingthe'Searchterms'(below)and
thegenename(STPG2isusedasanexample)
•
Foreachsearch,onlythefirstpageofresultswasconsidered.Searchresultsmostconsistentwithallsearch
termsarerankedbypage,thusthemostrelevantresultswerealwaysonthefirstpage.Thisapproachwas
alsoemployedtokeepthisliteraturesearchtractableintermsoftime(i.e.asearchforeachoftheterms
belowforonegeneusuallytook~1hour).
•
WealsousedtheGWASCatalog(https://www.ebi.ac.uk/gwas/)usingthegenenametosearchforfurther
potentiallinkstofitnessrelatedtraits
Searchterms(exampleusinggeneSTPG2):
•
"STPG2"and"reproduction"andgeneand-"noncommercialuse,distribution,andreproductioninany"
•
"STPG2"and"fitness"andgene
•
"STPG2"and"fertility"andgene
•
"STPG2"and"menarche"andgene
S32
Table S6
•
•
•
•
•
•
•
•
"STPG2"and"menopause"andgene
"STPG2"and"birth"or"birthweight"
"STPG2"and"pregnancy"andgene
"STPG2"and"placenta"andgene
"STPG2"and"implantation"andgene
"STPG2"and"oocyte"andgene
"STPG2"and"sperm"andgene
"STPG2"and"testis"
References
1.
2.
3.
4.
Zuccotti,M.,etal.,MaternalOct-4isapotentialkeyregulatorofthe
developmentalcompetenceofmouseoocytes.BMCDevelopmentalBiology,
2008.8(1):p.1-14.
Sun,P.R.,etal.,Genome-wideprofilingoflongnoncodingribonucleicacid
expressionpatternsinovarianendometriosisbymicroarray.FertilSteril,2014.
101(4):p.1038-46e7.
Janowski,D.,etal.,Incidenceofapoptosisandtranscriptabundanceinbovine
follicularcellsisassociatedwiththequalityoftheenclosedoocyte.
Theriogenology,2012.78(3):p.656-659.
Enquobahrie,D.A.,etal.,Maternalperipheralbloodgeneexpressioninearly
pregnancyandpreeclampsia.IntJMolEpidemiolGenet,2011.2(1):p.78-94.
S33