Instruct: Identify the main and secondary category of Arxiv papers based on the titles and abstracts
Query: Prediction and replication from case-control sequencing studies using
  custom genotyping and additional sequencing   We present two results about using allele-count (AC) burdens of rare SNPs
discovered in a case-control sequencing study for prediction or validation in
an external prospective study. When genotyping only the SNPs polymorphic in the
sequence data, the phenotype to AC correlation tends to be larger in the
replication data than the primary study. Conversely, if the replication sample
is sequenced, ACs of SNPs which are novel in the replication tend to have much
smaller or opposite signed associations. We explain this by first deriving the
AC-phenotype association implied by a model of diverse SNP effects, and second
accounting for the shifted distribution of SNP effects when using a
case-control study as a filter for SNP inclusion. In rare diseases, the case
population is depleted of protective SNPs and enriched for deleterious SNPs,
creating the above difference in AC associations. This phenomenon is most
relevant in re-sequencing for risk prediction in rare diseases with
heterogeneous rare mutations because it applies to SNPs with MAF near 1 out of
the case-control sample size and is exaggerated when SNP log-odds ratios come
from a heavy-tailed distribution. It also suggests a ``winner's curse'' in
which most risk increasing SNPs at a particular MAF are quickly discovered and
future sequencing finds more protective or irrelevant SNPs.

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The categories of this paper are: gr-qc
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The categories of this paper are: cs
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The categories of this paper are: math-ph
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The categories of this paper are: physics
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The categories of this paper are: quant-ph
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The categories of this paper are: atom-ph
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The categories of this paper are: cond-mat
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The categories of this paper are: math
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The categories of this paper are: nlin
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The categories of this paper are: hep-ph
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The categories of this paper are: ao-sci
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The categories of this paper are: alg-geom
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The categories of this paper are: hep-lat
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The categories of this paper are: econ
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The categories of this paper are: dg-ga
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The categories of this paper are: plasm-ph