Parkinson's disease organization

[sbello]

I think we should review the organization of the Parkinson's disease branch. I was trying to define the difference between juvenile onset and early onset Parkinson's. I found in https://www.ncbi.nlm.nih.gov/pubmed/25904081 a definition for early onset that is onset of motor symptoms before 40 years of age. In OMIM 2 of the juvenile subtypes (615528, 606693) have onset in the 1st or 2nd decade of life but the third, 600116, has onset before 40. If juvenile onset is defined as 'in the 1st or 2nd decade of life' then the third example should not be under this branch despite being named 'juvenile'. But the text of the OMIM entry states 'An autosomal recessive form of familial juvenile parkinsonism, defined as onset before age 40 years, was described in a Japanese family by Takahashi et al. (1994).' The Orphanet entry for 'Atypical juvenile parkinsonism' (ORPHA:391411) has two OMIM xrefs (615528 615530) one of which is 'early onset' in OMIM. I would suggest obsoleting 'juvenile-onset Parkinson's disease' (DOID:0060893) and moving the children of this term to be under early onset (DOID:0060894). Then define early-onset as: 'A Parkinson's disease characterized by onset of motor symptoms prior to 40 years of age.' dbxref: url:https://www.ncbi.nlm.nih.gov/pubmed/25904081 Late onset (DOID:0060892) would then be defined as 'A Parkinson's disease characterized by onset of motor symptoms after 40 years of age.' dbxref: url:https://www.ncbi.nlm.nih.gov/pubmed/25904081

[sbello]

Note ORPHA:2828 Young-onset Parkinson disease has the synonym of early onset and lists the age of onset as 'between 21-45 years'. So possibly juvenile onset could be before 21 years? But Orphanet also has OMIM terms with age of onset of 50+ xreffed to ORPHA:2828

[lschriml]

Hello Sue, Great idea to re-assess this classification. I agree, these terms need to be re-evaluated, so that we have consistent categories. It would be great to have defined age limits for each category that we can all use.

I'm good with the ranges being: < 21 - juvenile 21-40 - early onset

40 - late onset

Across resources there seems to be agreement about juvenile-onset : before 21 years of age I haven't found consensus about the range for early-onset: resources vary --> the top of the range may be 40 or 45.

I would suggest we connect plan the re-classification and then get in touch with Joanna and Ada and get their input on our planned re-classification.

Looks like this was a hot topic in these 2015 - 2016 papers:

The paper (above) : --> definition: https://www.ncbi.nlm.nih.gov/pubmed/25904081 a definition for early onset that is onset of motor symptoms before 40 years of age

I had a look at their source for the definition of early onset: A Schrag, JM Schott. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism Lancet Neurol, 5 (2006), pp. 355-363

--> defn: The clinical phenotype associated with this mutation is similar to that of classic Parkinson’s disease, apart from early onset (on average in the fourth decade).

--> Interesting that the two are not the same.

This got me curious, so I hunted around a bit further; I found in: https://www.ncbi.nlm.nih.gov/pubmed/27221269 CMAJ. 2016 Nov 1;188(16):1157-1165. doi: 10.1503/cmaj.151179. Epub 2016 May 24. Title: An update on the diagnosis and treatment of Parkinson disease.

[PDF link]
--> top of the 2nd page:

The onset of Parkinson disease can be categorized as juvenile (age < 21 yr), early onset (21–50 yr) and late onset (generally > 60 yr).2

And in Orphanet: https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=932&Disease_Disease_Search_diseaseGroup=ORPHA-2828&Disease_Disease_Search_diseaseType=ORPHA&Disease(s)/group%20of%20diseases=Young-onset-Parkinson-disease&title=Young-onset%20Parkinson%20disease&search=Disease_Search_Simple

Young-onset Parkinson disease (YOPD) is a form of Parkinson disease (PD), characterized by an age of onset between 21-45 years

Cheers, Lynn

[sbello]

Once we work this out with OMIM we should also get in touch with Orphanet as I've come across multiple OMIM terms that I would put under late onset that Orphanet has mapped to early onset. I did email Joanne about several of the OMIM ones I reviewed today as it was not clear to me why these were in as 'disease' entries and not 'susceptibility to disease' entries. The references mostly referred to these as susceptibility or risk loci. I'll let you know what I hear from her. Should we add this to the agenda for next Thursday's call?

[lschriml]

Yes, this is a good topic for Tuesday. It’s great that you are leading the effort to untangle these terms.

Cheers, Lynn

Sent from my iPhone

On May 3, 2019, at 3:51 PM, Sue Bello notifications@github.com wrote:

Once we work this out with OMIM we should also get in touch with Orphanet as I've come across multiple OMIM terms that I would put under late onset that Orphanet has mapped to early onset. I did email Joanne about several of the OMIM ones I reviewed today as it was not clear to me why these were in as 'disease' entries and not 'susceptibility to disease' entries. The references mostly referred to these as susceptibility or risk loci. I'll let you know what I hear from her. Should we add this to the agenda for next Thursday's call?

— You are receiving this because you commented. Reply to this email directly, view it on GitHub, or mute the thread.

[sbello]

Reply from Joanna at OMIM to the question of why these were disease entries and not susceptiblity to disease entries: PARK16 (613164) and PARK12 (300557) are Parkinson disease loci. If/when a gene is found to be functionally associated with this locus, we would closely evaluate the penetrance.

Because these are loci, not functional relationships, does it matter?

[sbello]

Follow up from Joanna: It is possible (even likely) that nothing will ever come of these entries. Why enter them in DO? Patients either have Parkinson disease or they don't. I remember Dr. McKusick expressing some reluctance about putting "susceptibility" on a title. This happened because there were people who misunderstood MIM titles especially for common diseases and we had to put the brakes on somehow. Some entries that that are based on GWAS (there aren't many and the are confined to certain topics) may also have susceptbility.

[sbello]

I've put together a Google spreadsheet with the DO terms, OMIM records and what is stated about age of onset https://docs.google.com/spreadsheets/d/1oq1gfl-sVu2RLgRGxpJIAhRm3KdKV0tBkebLfSAM3lo/edit?usp=sharing Joanna offered to chat with me/us about this. I think it would be useful to have a discussion about how we should handle and parse the '%' and 'blank' OMIM records in DO. It maybe advisable to not cross-reference in DO OMIM records for disease 'subtypes' that don't have any gene. These may just not really have enough information to accurately enter into DO.

[lschriml]

Lets set up a call with Joanna - good idea to coordinate.

Cheers, Lynn

On Mon, May 6, 2019 at 2:53 PM Sue Bello notifications@github.com wrote:

I've put together a Google spreadsheet with the DO terms, OMIM records and what is stated about age of onset https://docs.google.com/spreadsheets/d/1oq1gfl-sVu2RLgRGxpJIAhRm3KdKV0tBkebLfSAM3lo/edit?usp=sharing Joanna offered to chat with me/us about this. I think it would be useful to have a discussion about how we should handle and parse the '%' and 'blank' OMIM records in DO. It maybe advisable to not cross-reference in DO OMIM records for disease 'subtypes' that don't have any gene. These may just not really have enough information to accurately enter into DO.

— You are receiving this because you commented. Reply to this email directly, view it on GitHub https://github.com/DiseaseOntology/HumanDiseaseOntology/issues/702#issuecomment-489733542, or mute the thread https://github.com/notifications/unsubscribe-auth/ABBB4DNYWMOVC3UOEPFMQJLPUB5DHANCNFSM4HKV73IA .

-- Lynn M. Schriml, Ph.D. Associate Professor

Institute for Genome Sciences University of Maryland School of Medicine Department of Epidemiology and Public Health 670 W. Baltimore St., HSFIII, Room 3061 Baltimore, MD 21201 P: 410-706-6776 | F: 410-706-6756 lschriml@som.umaryland.edu

[sbello]

After talking with Joanna, the suggestion is to:

1. separate gene specific disease subtypes from the age of onset groupings, many times the same gene may be associated with variable age of onsets
2. drop early/late/juvenile modifiers from disease names, according to Joanna OMIM will include helpful information after a comma in the OMIM title that is not necessarily part of the disease 'name' 3.leave out the ambiguous entries where there is not enough information to make the call between a disease subtype and a susceptibility locus

[sbello]

The result of this is that the IDs below will not be incorporated into DO for now. If the records are updated to clarify the meaning of these entries we will revisit this decision. OMIM:300557 OMIM:613164 OMIM:606852

[lschriml]

Three upper level parents: juvenile, early, late genetic types (OMIM) name by #

[lschriml]

Parkinson's disease early onset (merge in juvenile onset)

 -- OMIM genetic terms

late onset: OMIM: 
                 168600 (move from Parkinson's disease ) 

[sbello]

These changes are all in so I'm closing this.