NCRAD Update

1
NCRAD Update
Tatiana Foroud, Ph.D. Indiana University
2
Identify Appropriate Families Send Columbia a
Preliminary Pedigree Obtain samples/complete
study visits Transfer Minimal Datatset to
NCRAD Send Columbia the Sampled Pedigree
3
Identify Appropriate Families
4
Appropriate Families for Study

• At least 2 living siblings with LOAD (onset gt 60
  years)
• At least 1 other living related family member who
  
• Has AD (onset gt 50 years)
• Or
• Is unaffected (gt 60 years)

5
Who to collect?

• Genetic analysis seeks to study the transmission
  of marker alleles throughout the family.
• When we can determine the inheritance of all
  marker alleles unambiguously, we have the
  greatest power to find genes for disease!
• Unaffected individuals may be very important for
  collection.

6
Which are the best families?

• Families with the largest number of affected
  individuals.
• Strong family history suggests more genetic
  effects.
• Unaffected individuals in families with many
  affected individuals are also very important,
  particularly if they are examined clinically.

7
Who to Collect

• Collect the parents in generation I, if available
• Collect all siblings in generation II (affected
  and unaffected)
• Collect any individuals in generation III with
  memory loss
• Collect any individuals in generation III gt 50
  years
• Query for any other affected cousins, half
  siblings, aunts, uncles??

I
II
III
8
Unaffected Individuals

• We focus the collection of unaffected individuals
  on those
• Over the age of 50 years
• Willing to undergo a cognitive evaluation
  (telephone or in person)
• Siblings and offspring of affected individuals
• Some others very much want to participate use
  judgment!

9
Preliminary Pedigree
10
The Preliminary Pedigree

• Is sent to the Coordinating Center at Columbia
  and should include
• Diagnosis
• Current age
• Age at onset
• Who will likely be sampled
• It is highly recommended to include the family
  and individual number.

11
Data Collection
12
Study Visit/Data Collection

• Based on recommendations from the Coordinating
  Center
• Samples and study visits are collected from all
  targeted individuals who are willing to
  participate

13
Minimal Dataset
14
Minimal Dataset

• A minimal dataset must be completed for all
  individuals from whom a biological sample has
  been sent to NCRAD
• Includes deceased individuals when an autopsy
  specimen is being sent

15
Minimal Dataset

• The minimal dataset is transferred each quarter
  to Indiana University. The contact person is
• Michael Daubs, Database Manager
• email mdaubs_at_iupui.edu
• tel [phone]

16
Sampled Pedigree
17
The Sampled Pedigree

• Is sent to the Coordinating Center at Columbia
  and should include
• All individuals identified by their family and
  individual number.
• Who was sampled.
• Who had a minimal dataset collected.
• Who had neuropsychological testing

18
Sampled Families

• A family cannot be considered completed or
  sampled until the minimal dataset is
  transferred to NCRAD for all biologically sampled
  individuals
• This is essential, since without the minimal
  dataset, we can determine whether the family
  meets the study criteria

19
Pedigree Sample Reports
Fam ID Ind ID Sample at NCRAD? Data Set at NCRAD? Need Data? Comments
601 19 Yes Yes No  
601 20 Yes Yes No  
601 32 Yes No Yes Need data
601 33 Yes No Yes Need data
601 21 No Yes No  
601 22 Yes Yes No  
601 23 No Yes No  
20
Pedigree Sample Reports
Fam ID Ind ID Sample at NCRAD? Data Set at NCRAD? Need Data? Comments
565 9 No Yes No  
565 7 Yes Yes No  
565 10 No Yes No  
565 26 Yes No Yes Have sample, not on pedigree, no data set on file.
21
Pedigree Sample Reports

• NCRAD sends out this report after receiving a
  copy of the sampled pedigree.
• This report highlights missing data that is
  required for a family to be considered sampled or
  complete.
• Important for sites to respond and submit missing
  information

22
Qualified Families Based on Submitted Data

• 205 families have a minimal dataset submitted to
  NCRAD for at least one family member
• Only 90 families consist of
• At least 2 siblings with a minimal dataset
  supporting AD
• At least one other biologically related family
  member meeting the age requirements and with a
  minimal dataset

23
Qualified Families Based on Submitted Data

• In the majority of families who do not qualify,
  the problems are
• A minimal dataset has not been submitted for the
  critical individuals
• Missing variables in the minimal dataset preclude
  the family from qualifying
• There are a small number of families who will
  never qualify. NCRAD and Columbia should be
  informed when the sampled pedigree is submitted

24
Samples to Researchers

• Researchers can request LOAD samples
• At this time, with only limited MDS data, no
  requests have been processed
• MTA out would be required
• Requests for samples should include
• IRB approval for proposed analyses
• Investigator CV
• Short description of proposed studies

25
Minimal Dataset and Sampled Pedigree

• These are both critical elements that the site
  must submit.
• Without both of these elements, NCRAD and
  Columbia can not determine if a family meets LOAD
  criteria.
• Without both of these elements, the family will
  not be as useful to researchers!