%PDF-1.5
%
618 0 obj
<>/Metadata 1248 0 R/Names 617 0 R/OpenAction 73 0 R/Outlines 9 0 R/PageMode/UseNone/Pages 124 0 R/Type/Catalog/ViewerPreferences<>>>
endobj
1248 0 obj
<>stream
application/pdf
Roman Teo Oliynyk
For more than a decade, genome-wide association studies have been making steady progress in discovering the causal gene variants that contribute to late-onset human diseases. Polygenic late-onset diseases in an aging population display the risk allele frequency decrease at older ages, caused by individuals with higher polygenic risk scores becoming ill proportionately earlier and bringing about a change in the distribution of risk alleles between new cases and the as-yet-unaffected population. This phenomenon is most prominent for diseases characterized by high cumulative incidence and high heritability, examples of which include Alzheimer's disease, coronary artery disease, cerebral stroke, and type 2 diabetes, while for late-onset diseases with relatively lower prevalence and heritability, exemplified by cancers, the effect is significantly lower. Computer simulations have determined that genome-wide association studies of the late-onset polygenic diseases showing high cumulative incidence together with high initial heritability will benefit from using the youngest possible age-matched cohorts. Moreover, rather than using age-matched cohorts, study cohorts combining the youngest possible cases with the oldest possible controls may significantly improve the discovery power of genome-wide association studies.
Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-wide Association Studies of Late-onset Diseases
2019-07-05T10:08:35+12:00
LaTeX with hyperref package
2024-03-28T06:48:33-07:00
2024-03-28T06:48:33-07:00
GWAS; genome-wide association studies; genetics; polygenic risk score; heritability; late-onset disease; simulation; gene variant; SNP
pdfTeX-1.40.18
False
This is MiKTeX-pdfTeX 2.9.6300 (1.40.18)
uuid:2773ef90-1dd2-11b2-0a00-3809275dc400
uuid:2773ef94-1dd2-11b2-0a00-810000000000
endstream
endobj
617 0 obj
<>
endobj
73 0 obj
<>
endobj
9 0 obj
<>
endobj
124 0 obj
<>
endobj
74 0 obj
<>
endobj
444 0 obj
<>
endobj
550 0 obj
<>
endobj
581 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
582 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
583 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
584 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
585 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
586 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
587 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
588 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
589 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
590 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Type/Page>>
endobj
591 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Type/Page>>
endobj
592 0 obj
<>/ProcSet[/PDF/Text]>>/Rotate 0/Type/Page>>
endobj
1296 0 obj
<>stream
HTMo80Gh=5i
vA=I`lbW~4
Լ7oΖ5"bPo2+MKRu?oE% xXck}?#PUqX2JJW8@Cv0%\>bBAjD
-Ɖ:=OlfhY2ຕ?:eࠉ)iX(J!!L؝VϏūD~ķ[Wx.ntazXM
>gp67tt]J%~o!~N[;W\c)|zڻ$NJIi%unI
)S~u
QqKSSJɕ\b >uёDCC2 ewַuҭ 6"Ǡ iw}x#^;<-%4ܤDphzh"鷇+3'=[{L;,1]xE#);v镊pV٤mX#~6abΙCW
x1=ˑ_0vH=cT0_)4!ׄveKiJ<FD\Sl39T077cO0 &
endstream
endobj
628 0 obj
<>
endobj
627 0 obj
<>
endobj
631 0 obj
<>
endobj
803 0 obj
<>
endobj
1253 0 obj
<>
endobj
828 0 obj
<>
endobj
829 0 obj
[505.9 0 0 0 0 0 0 0 0 0 0 0 0 786.9 786.9]
endobj
830 0 obj
<>stream
x}RiXSg"G(SQRJY
K1*`Cr\7VFJXEB "`bYّPۙ>;9=ygB A
Y(