Abstract
Provide
a one-page synopsis of the issues discussed in the
items below with a brief statement on each of these
items. Supply keywords, including the name(s) of the
gene(s), the name(s) of the disease(s) or disorder(s), and the word “epidemiology.”
Gene(s)
Identify
the gene(s) being reviewed and provide a brief
review of chromosome location, gene product, and
function, if known.
Gene
variants
List
known allelic variants with effects on function if
known, and summarize known information on the
frequency of homozygosity and heterozygosity of
these variants in different populations and ethnic
groups. The strategy used to identify relevant
papers should be specified, including the databases
searched and the period of publication considered.
Brief details of any hand searches should be given.
The summary of variation in genotype frequency
should include a table and a commentary on this in
the text. The date of preparation of the table
should be indicated in a footnote on each page. It
is recommended that the following information be
included:
Geographic
area in which the study was carried out.
Provide a brief description of how the subjects
whose genotypes were determined were sampled, e.g.,
subjects selected randomly from a population-based
sampling frame, blood donors, hospitalized subjects
(give reasons). When possible, the description
should include the mean age (standard deviation) or
age range and the distribution by gender. If the
subjects were controls from a case-control study,
the disease under investigation and any matching
criteria should be specified (e.g., subjects matched
to lung cancer patients on age, sex, and smoking
history). When relevant, the ethnic group should be
specified.
If
genotyping in a substantial proportion of studies
was inferred on the basis of phenotypic tests, these
studies should be grouped in a specific section of
the table. If more than one type of test was used, a
column should be used to indicate the type of test
used in the study.
Number
of subjects whose genotypes were determined.
When there are multiple alleles, those tested for
should be specified.
Genotype
frequency, with 95 percent confidence interval.
Whenever possible, genotype frequency should be
presented in preference to allele frequencies. For
two allele systems, when it is firmly established
that heterozygotes and homozygotes for the common
allele have similar enzyme levels, it is sufficient
to present the frequency of homozygotes for the
variant allele. When genotype-enzyme level relations
are not well established, we suggest presenting the
frequency of homozygotes for the variant allele and
heterozygotes in separate columns.
For
multiple allele systems, when genotype-enzyme level
relations are well established, grouping may be made
on the basis of inferred phenotype. When genotype-
enzyme level relations are not well established, we
suggest presenting the frequencies of homozygotes
for the most common variant. Inclusion of
frequencies of other genotypes will depend on the
range of alleles investigated in the studies
included in the review.
The
in-text reference should be specified in the
following format: single author—last name, year of
publication (reference number); two authors—last
name 1 and last name 2, year of publication
(reference number); more than two authors—last
name et al., year of publication (reference number).
It
is suggested that order of the articles reviewed be
first by continent or major geographic area (e.g.,
Americas, Africa, Asia, Europe, Oceania) and then
alphabetically by location
within country (multicenter studies and studies in
which the location within the country is not
specified first). This order makes it relatively
easy to see sequential publications relating to the
same population.
Disease(s)
or
other outcomes
Identify
the disease(s) or other outcome(s) with which the Gene(s)
is/are associated. Briefly summarize the descriptive
epidemiology and confirmed and suspected risk
factors (including other genes).
Associations
As
it is likely that the search strategy will have been
similar to that for the distribution of the relevant
genotypes in different populations and ethnic
groups, it will normally be sufficient to
cross-refer to the strategy described in the section
on Gene variants and state what additional headings
and text words relevant to the disease or other
outcome have been added. Summarize the magnitude of the
association between the allelic variants and various
diseases in terms of absolute, relative, and
attributable risks in different populations. Comment
on the quality and methodology of studies.
Especially for studies of the association between
genetic polymorphisms postulated to affect
susceptibility, it may be helpful to summarize the
studies in a table in the following format:
Geographic
area in which the study was carried out and period
of recruitment of study subjects.
Case
type and number.
The type should include the condition under
investigation (so that differences between studies
can be identified), the method of ascertainment
(e.g., register, one hospital, several hospitals,
family practitioners), age range, gender
distribution, and, if available, participation rate.
If a nested case-control or case cohort design was
used, this should be specified.
Controls
(or cohort) type and number.
Sufficient information should be given for the
reader to understand whether cases and controls were
derived from the same source population, with
similar eligibility criteria, and whether matching
was carried out. (If matching was used, the matching
variables should be specified).
For
loci for which there are multiple alleles, the
alleles investigated and the comparison to which the
relative risk estimate relates should be specified.
It is possible that ad hoc calculations will have to
be made from the information presented to enable
comparison between studies. When this has been done,
it should be noted, e.g., by enclosing the relative
risk in square brackets.
When
the studies of genotype-disease associations have
been carried out in a limited number of geographic
areas or if selection bias is thought to be an issue
in the interpretation of these studies, it may be
helpful to include a column specifying the
population of controls with the genotype to which
the primary hypothesis relates.
Relative
risk and 95 percent confidence interval for the
stated comparison.
When adjustment has been carried out, these should
be specified. When no estimate is presented and
insufficient data are presented for calculation, but
the authors have commented on an association, this
should be stated.
For
some genotype-disease associations, subgroup
analyses have been reported. So far, the statistical
power of many of these analyses has been low. It may
be helpful to include a column indicating what
sub-groups have been analyzed (e.g., subsite of
tumor, tumor histology, age, ethnic group), but
discuss the results in the text rather than trying
to summarize all subgroup analyses in a table.
Brief
details of any exposure assessment carried out to
investigate possible interaction (effect
modification) should be included.
The
results of any analysis of possible interaction
(effect modification) should be summarized..
The in-text reference should be specified in the
format already described.
Interactions
Discuss
whether the allelic variants interact with any of
the known risk factors for the disease, including
other genes and environmental factors. Summarize the
magnitude of such interactions.
Laboratory
tests
Summarize
the sensitivity, specificity, and positive and
negative predictive values (including 95 percent
confidence intervals) of different tests available
for the gene(s), including biochemical, molecular,
and other tests in different populations. Summarize
the type of study subjects in which the analytic or
clinical validity of the tests were investigated.
Population
testing
Summarize
population-specific data on the magnitude and
determinants of testing for allelic variants of the
gene(s) and the impact of testing on public health
(morbidity, mortality, disability), including policy
statements, recommendations, and legislation
(including mention of available interventions). This
section should summarize the quality of evidence
regarding population testing and any associated
intervention that might affect the relation between
the gene and the disease.
Other
potential public health applications
Summarize
potential public health applications of human genome
epidemiologic information on the variants of the
gene(s), e.g. setting permissible exposure
thresholds, including quality of information.
Conclusions
and recommendations for research.
Strengths
and gaps in the evidence base regarding the public
health implications of human gene variants should be
identified. Recommendations should be made to
stimulate research to fill the gaps.
References
(according to journal format)
Internet
sites
Include
relevant links to various genetics databases, online
resources, educational materials, consensus
statements, policy statements, and support groups.
