Older siblings and Parkinson’s disease

Curious new research results out of Sweden this weekend…

To all of our readers who have older siblings that you grew up fighting with – you should  go and give them a hug today, because apparently they have lowered your risk of Parkinson’s disease.

Like I said ‘curious’.

---

Source: Buzzfeed

Older siblings. Nothing but trouble (a bit like younger siblings now that I think about it).

Who needs them.

Well, according to a massive new epidemiological study from the Karolinska Institutet, Stockholm (Sweden), we all do!

Title: Early-Life Factors and Risk of Parkinson’s Disease: A Register-Based Cohort Study.
Authors: Liu B, Chen H, Fang F, Tillander A, Wirdefeldt K.
Journal: PLoS One. 2016 Apr 15;11(4):e0152841.
PMID: 27082111      (This article is OPEN ACCESS if you would like to read it)

This is a fascinating study, not only in its size and scale, but for the interesting details in the results.

The investigators collected a huge amount of information from multiple nationwide Swedish registers that are cross-linked thanks to the national personal identification number system that is used in Sweden (each Swedish resident is assigned a unique number).

Stockholm, the capital of Sweden. Source: Budgetyourtrip

The information was collected from:

• The Swedish Multi-Generation Register (MGR) – which holds information about the biological and adoptive parents for all residents born in 1932 or later, and were alive or lived in Sweden in 1961. This database covers over 95% of Swedish-born residents, plus more than 22% of foreign-born residents in Sweden.
• The Swedish Patient Register – established in 1964/1965, this databases collects inpatient discharge records. It became nationwide in 1987, and since 2001, the Patient Register has recorded information on every inpatient visit and vast majority of the outpatient visits for all Swedish residents. 
• They also linked their data to the Migration Register and Swedish Population and Housing Censuses from 1960, 1970, 1980, and 1990 for information on socio-economic status.

Like I said, ‘a huge amount of information’. They next set up a selection criteria. Within their pool of people for analysis, individuals had to:

• be born in Sweden between 1932 and 1970
• have information available regarding maternal links in the MGR
• be alive and free of Parkinson’s disease on January 1, 2002,
• 40 years or older on January 1, 2002 or turned 40 years during the study period

3 545 612 people fulfilled this criteria. 8779 cases of Parkinson’s disease were identified within that population of people (a further 2658 people were identified as having Parkinson’s disease, but since they were diagnosed before 2002, they were excluded). When looking at the findings of the analysis of this study:

Unsurprisingly:

• the average age of diagnosis was 65.1 years of age
• males had a higher risk than females (1.5 times more men than women)
• parental occupation as farmers increased risk of Parkinson’s
• a family history of the condition results in a higher risk of Parkinson’s disease.
• No difference between blue or white collar occupations, or self employed roles
• No difference between month/season of birth
• No association with early life factors, including flu burden in the year of birth.

Surprisingly:

Compared to those without older siblings, the risk of developing Parkinson’s disease was 7% lower among participants with older siblings (HR = 0.93, 95% CI: 0.89, 0.98). The number of people with no older siblings was 1.68 million, of which 5384 had Parkinson’s disease. But of those with older siblings (1.86 million) only 3395 had Parkinson’s disease. Curiously, however, there was no further associations (eg. the number of older siblings or the interval length between the individual and their older siblings).

The effect (7%) is small, but the number of cases is very large, so we can assume that the finding is real. But how to explain it?!?

Even more surprisingly:

This is not the first time we’ve seen something like this:

Title: Maternal age, exposure to siblings, and risk of amyotrophic lateral sclerosis.
Authors: Fang F, Kamel F, Sandler DP, Sparén P, Ye W.
Journal: Am J Epidemiol. 2008 Jun 1;167(11):1281-6.
PMID: 18367467

In a similar sort of study published in 2008 (also from researchers at the Karolinska Institute in Sweden), it was reported that the risk of amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s disease; another neurodegenerative condition) increased with the number of younger siblings, and children whose first younger sibling was born after the age of 6 years had the highest risk of ALS. In contrast to the Parkinson’s research above, however, exposure to older siblings was not associated with an increased risk of ALS.

And a similar sort of result has also been observed in cases of Schizophrenia:

Title: Exposure to prenatal and childhood infections and the risk of schizophrenia: suggestions from a study of sibship characteristics and influenza prevalence.
Authors: Westergaard T, Mortensen PB, Pedersen CB, Wohlfahrt J, Melbye M.
Journal: Arch Gen Psychiatry. 1999 Nov;56(11):993-8.
PMID: 10565498

This research came from a different Scandinavian capital (Copenhagen), and involved only 1.74 million people, but it suggested that larger sibships were associated with an increased risk of developing schizophrenia. This result was independent of birth order or interval length between siblings. 

Why these effects exist is a question yet to be answered. In each of these studies, the authors propose elaborate possibilities (eg. developmental theories involving the immune system, etc), but there is no evidence (yet) to support them. Given that the effects are small (just a 7% reduction in risk in the case of Parkinson’s), it would be interesting to investigate differences between subjects within the Parkinson’s population, to determine if there is a subset of individuals more affected than others by this sibling phenomenon. By comparing which commonalities they may share (genetic, environmental or otherwise) we could identify patterns of risk factors for specific individuals.

So while the Parkinson’s connection is an interesting finding, obviously more research is required to better understand what is going on.

Curious result though, right?