MRC Institute of Genetics and Molecular Medicine wwwigmmacuk GS Symposium 6 th May 2016 Caroline Hayward Quantitative Trait Genetics in Health and Disease 20032 GSSFHS DNA samples genotyped and passed quality control with Illumina OmniExpress Exome chip at WTCRF Genetics Core lab ID: 590421
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Medical Research Council Human Genetics UnitMRC Institute of Genetics and Molecular Medicinewww.igmm.ac.uk
GS Symposium6th May 2016
Caroline Hayward
Quantitative Trait Genetics in Health and DiseaseSlide2
20,032 GS:SFHS DNA samples genotyped and passed quality control with Illumina Omni-Express + Exome chip (at WTCRF Genetics Core lab, Edinburgh) (Ancestral outliers removed)
951,117 SNPs assayed, with low sample failure and high call rates870 DNAs that have been exome sequenced, primarily for analyses of depression and cognition or extremes of obesity;
family representatives, and parent-child trios & quads Funded by MRCHGU * and Wellcome
Trust (STRADL)**
*
**
*
Phase1* Phase2* Phase3**
Genotype
QC and SummariesSlide3
Efficient haplotype determinationSegregation of diseases and/or traits within families *Allow family-based linkage-type analyses Allow parent-of-origin analyses *
Enrichment for carriers of rare or novel variants Allow
de novo mutation discoveryHelps prediction and verification of sequence-identified variants (by imputation)
Value of Family data in
genome-wide genetic analysesSlide4
Genetic kinship annotated with self-reported Social PedigreeGenetic kinship annotated with corrected* Social Pedigree
P of sharing 0 alleles IBDP of sharing 1 alleles IBD
P of sharing 0 alleles IBD
P of sharing 1 alleles IBDTwins
Full Sibs
Parent-Child
Other related
Half Sibs
Unrelated
Social Pedigree Correction
*Corrections done by checking genetic relationships and questionnairesSlide5
Parent-childFull sibsHalf sibs
Cousins
Avuncular
Grandparent
9853
8495
381
2443
6599
848
Number genotyped
Males
Females
20032
8227
11805
Full Cohort
Pedigree size
Families
Family size
Generations
Average
Maximum
Average
Maximum
42662
6863
6
66
2.34
5
Genotyped IDs
Generation Scotland Family Summaries
Genotyped Pairs
(23960 without dummies)Slide6
Manhattan Plot GS 20K serum creatinineSLC34A1FBXO47Slide7
NASODIUM10974148254KPOTASSIUM10871
144156UREAUREA10859
140794CRE
CREATININE10853140103
eGFR
ESTIMATED GFR
10716
102709
eCOM
CKD Stage
10573
97539
CHOL
TOTAL CHOLESTEROL
10523
57594
HDL
HDL-CHOLESTEROL
10505
54371
CHR
TOTAL CHOL/HDL-CHOL
10496
55169
GLP
GLUCOSE (preserved tube)
10324
45257
Laboratory data on 10,943 unique Tayside participants was released by HIC to the Tayside Safe Haven for use by
GS (May 2014).
Increased to 11,125 participants (September 2015)
Baseline measures:
University of Dundee Health Informatics Centre (HIC)
Data ReleasesSlide8Slide9
Uric acid data cleaning/selectionStandardise units to µmol/LSelect highest reading per IDRemove pregnant women (117)2,238 individuals with single measure collected from Oct 1988 to August 2015Date of test noted for age adjustment in association analysis.
Pilot study: Uric Acid from NHS biochemistry recordsSlide10
SLC2A9GWAS of Uric Acid from NHSSlide11
Research Collaborations
VIKING HEALTH STUDY
(Orkney & Shetland)
GENERATION SCOTLAND
(Scottish Family Health Study)
LOTHIAN BIRTH COHORTS
(1921 & 1936)
Scotland
IGMM
MRC HGU
CGEM
Usher Institute
Lynne Hocking, Alison Murray
(Aberdeen)
Blair Smith,
(Dundee)
Christian
Delles
, Ruth
Jarrett, Naveed Sattar
(Glasgow)
David
Porteous, Ian Deary
, Andrew McIntosh, Helen
Colhoun
(Edinburgh)
Viking Health Study
Lothian Birth Cohort
ROHgen
Ygen
LifeGen
UK
& Ireland
Martin
Tobin (Leicester
) SPIROMETA
Mark Iles (Leeds)
Mark
McCarthy,
Jonathan Marchini (Oxford)Tim Frayling (Exeter)CARTA Consortium (Bristol)UK BiobankSlide12
EUROPEUKEuropean Research Collaborations
EuropeIvana Kolcic, Tatijana
Zemonik,Ozren Polasek (Split, Croatia)
Yurii Aulchenko (Groningen, Netherlands)Olivier Devuyst, (Zurich, Switzerland)
Murielle Bochud , Zoltan Kutalik (Lausanne, Switzerland)
AGES Cohort,
Iceland
CROATIA-VIS
CROATIA-SPLIT
CROATIA -KORCULASlide13
UKEUROPEUSA
JAPANINDIA
AFRICA
CANADAWorldwide Research Collaborations
CHINA
INDONESIA
AUSTRALIA
Worldwide
CHARGE
CKDGEN
REPROGEN
Pfizer
CREAMSlide14
Publications resulting from GS dataSlide15
Thank youAll colleagues, collaborators and GS:SFHS participants