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| SardiNIA Study: Proposal for analyses                                 |
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| **Name and Institution of the proposing investigator.**               |
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| **Sponsoring responsible member of the steering committee**.          |
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|                                                                       |
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| **Descriptive title of the proposal.**                                |
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|                                                                       |
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**Guidelines for sharing genome-wide association results for
\[traits/diseases\]\-\-\-\-\-\-\-\-\-\-\--**

**Date:
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**1. Background and Overview**

Recent experience with genome-wide association (GWA) studies has shown
that increasing power is critical to making discoveries. In individual
genome-wide studies, associated variants may often show suggestive
evidence of trait association, but not rise to the top of any particular
list of results, due to the expected small effect sizes. By combining
lists of results, we expect that truly associated variants will rise
closer to the top of a combined list. Therefore, we agree to engage in a
collaboration to share results from genome-wide association studies of
quantitative traits to enable follow-up genotyping studies based on a
combined list of results, thereby increasing the likelihood of making
new discoveries.

**2. Participating groups and analysis plans**

Participating groups are listed below.

Participating groups will share genome-wide results for the specified
list of traits and/or diseases that they have in common or will generate
from their existing trait data. As currently planned, these include
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In addition, we agree to share current trait lists and subject counts
for each trait/disease, to determine if other traits can/should be
derived to increase overlap. If agreed to by participating groups,
additional traits/diseases can be added to this agreement. Participating
groups will share descriptions of the analyses they have done, including
data cleaning, transformations, and analysis methods, and will discuss
whether they might want to update procedures to be more parallel.

For each trait/disease, participating groups will share results for all
successfully genotyped markers in their primary GWA scan data. The
specific information to be shared will be selected to facilitate cross
study analysis, but will at a minimum include rs number, allele
designations, genotype counts, estimated effect sizes and confidence
intervals, and p-values for association tests, together with basic
descriptive summaries of the data. The initial analysis will be an
additive model, but other models and secondary analyses could be
performed if agreed to by the participating groups and would fall under
the same considerations described below.

In addition, where possible, association results for imputed SNPs in
HapMap will also be shared to facilitate analysis of additional SNPs and
particularly analysis across genotyping platforms. In order to receive
data on imputed SNPs, participating groups would be expected to
contribute results for imputed SNPs from their own study.

It would also be helpful to share quality control information: summary
counts of duplicate genotype inconsistencies, Mendelian inconsistencies,
and Hardy-Weinberg statistics for genotyped markers, when such
information is available.

The preferred approach for sharing data with the other participating
groups should be to

encourage their participation as partners in the consortium effort so as
to increase the likelihood of success of all our efforts and to minimize
the potential for conflicts of interest. Although individual groups may
choose to share their own data more broadly, they may not do so with
other groups' data or results without the agreement of all participating
groups.

Participating groups for this set of traits are expected to be:

a\.
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b\. SardiNIA study

With the agreement of all participating groups, additional participating
groups may be added subject to their agreement to abide by these
guidelines for sharing.

Each participating group may have confirmation samples at their disposal
either from their own studies or through collaborators. Participating
groups are authorized to share information with their collaborators only
as needed to allow follow up of interesting markers; collaborators will
be instructed that the information provided is confidential and to be
used only for the purpose of this follow up. For the purposes of this
agreement, collaborating groups that carry out follow up will be viewed
as part of the corresponding participating group rather than as
independent participating groups. Results from these follow up efforts
will be shared with the other participating groups.

Each participating group may also have access to additional GWA data,
and in some cases, there may not be an agreement to share these
additional GWA data among the participating groups. In this case,
participating groups would not be required to share their own GWA data
with the investigators who are providing the additional unshared GWA
data. A participating group with access to unshared GWA data may use
these additional data to further guide their experiments. However, the
participating group agrees to communicate with the other participating
groups about any actionable results, as described below. The principle
here is that interesting results that emerge from a combination of
unshared and shared data be treated the same way as if they arose
entirely from shared data.

**3. Publication plans**

This GWA sharing may result in interesting results immediately and will
also inform SNP selection for subsequent follow up genotyping. Once GWA
data are combined, we will discuss the results and plan how to go
forward with joint and/or parallel publications and/or follow up
genotyping. Publications could be organized by individual participating
groups (either one or multiple participating groups per publication)
and/or by (sets of) traits. The best approach is likely to be driven by
the results obtained, but the goal for the initial follow-up of GWA
studies (the first 1-2 waves of papers for each set of traits that are
based on shared GWA data) would be a small set of publications from the
consortium effort, based on related groups of traits. When multiple
consortium groups collaborate on a single publication, each of the
collaborating groups will have members included in the author list with
the aim of maximizing the contribution of each group as an equal partner
-- that is, most likely with multiple first and senior authors, with the
overall first and overall last authors from different partners. When
consortium participants proceed with multiple parallel publications, the
goal should be for these publications to be coordinated and cross
referenced. The approach for synchronizing publications will depend on
how well synchronized participating groups are in their plans. For
example, when synchronizing publications would require a delay of less
than a month, it would be considered bad form not to coordinate;
however, expecting a participating group to delay longer than three
months to synchronize submission would not be reasonable. Discussions of
publication plans should weigh both the value of stronger publications
(with larger stage 1 samples or evidence or more extensive replication,
for example), the need for rapid publication, and the principle of equal
partnership among the participating groups. This means that if data from
the consortium lead to an important result, but it is not possible to
synchronize publication plans, then all consortium members should be
represented in the authorship of the first publication.

**4. Communication**

All participating groups agree to keep the other participating groups
informed about follow up genotyping and corresponding results and to
coordinate publication plans. Specifically, participating groups agree
at a minimum to communicate with each other at the following times:

a\. when action is taken (for example, ordering primers for genotyping)
based on shared lists of results

b\. when an analysis is complete (with some degree of confidence) for
follow-up genotyping from shared lists of results

c\. when there is a proposal to modify publication plans substantially.

**5. Other uses of data**

Individual participating groups may identify other uses to which the
joint data may usefully be applied. All participating groups agree to
consult with the other groups before shared data are used for any
purpose not specifically agreed to here. No participating group data
will be used for another purpose without explicit approval from that
participating group. It is expected that each group may choose to do
further experimental work on genes or associations uncovered by the
consortium activities, and communications would be designed to minimize
or at least communicate about any overlapping or competing efforts.

representing

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

representing SardiNIA