🧬 Do Genes Determine If One Will Get Psoriasis? What Can You Learn from 23andMe Data?

What is Psoriasis?

Psoriasis is an autoimmune skin condition that causes rapid skin cell production which leads to the formation of thick, red, scaly patches on the skin. There are several types of psoriasis, each with distinct characteristics, but when the term psoriasis is used, it generally refers to psoriasis vulgaris, also known as plaque psoriasis.

Psoriasis vulgaris is the most common form of psoriasis, and it is manifested as red, raised, inflamed lesions covered with a silvery-white scale. These white silvery scales form plaques most commonly located on elbows, knees, scalp, and lower back but can appear anywhere on the body, and these scales can be itchy and even painful.

As I mentioned, there are other types of psoriasis, but psoriasis vulgaris accounts for about 80% to 90% of psoriasis cases.

As already mentioned, the term psoriasis can refer to any other type of psoriasis within the family of these conditions, such as: 

1. Guttate psoriasis: Characterized by small, dot-like lesions.

2. Inverse Psoriasis: Shows up as very red lesions in body folds, like behind the knee or armpit.

3. Pustular Psoriasis: Characterized by white pustules surrounded by red skin.

4. Erythrodermic Psoriasis: A rare, severe form causing widespread redness over most of the body. It can be life-threatening.

5. Psoriatic Arthritis: A condition where patients have both psoriasis and arthritis, affecting joints and skin.

What Causes Psoriasis?

Psoriasis is, as already mentioned, a complex autoimmune condition, but the exact cause is not fully known. However, what researchers have learned so far is that psoriasis probably results from a combination of the following:

1. Genetic 

2. Immunological, and 

3. Environmental factors. 

In this blog post, I will obviously exclusively focus on the genetic component of psoriasis. 

From what we know, psoriasis has a significant genetic component as researchers observed that people with a family history of psoriasis are more likely to develop the condition. 

Next, specific genes have been identified that are associated with the development of psoriasis, and I will cover this in more detail in the coming paragraphs of this post. However, having these genes does not guarantee that a person will develop the condition, as multiple genes need to interact to trigger psoriasis.

How Heritable Psoriasis Is?

According to a twin study [reference], genetics explains roughly 70% of susceptibility to psoriasis, which shows that psoriasis is justly described also as a complex genetic disease. 

Obviously, these heritability estimates (heritability refers to how much genetics explains out of total variation for a given condition, in this case, psoriasis) can significantly vary depending on the methodology being used, the type of psoriasis being evaluated as well as the structure and size of the population on which heritability estimation was done. However, in any case, we can firmly say that psoriasis has a solid genetic background.

What Genes and SNPs Are Associated With Psoriasis?

Since we now established that genetics, among other things (environment and immunology), determines the development of psoriasis, one would probably want to know what genetic variants (SNPs) and genes in which those variants are located are associated with the onset of psoriasis. 

For that purpose, I performed a short analysis where I acquired association data from the following large-scale genome-wide association studies focused on identifying genetic variants and genes being associated with psoriasis:

• Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in Japanese

• Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture

• A cross-population atlas of genetic associations for 220 human phenotypes.

• Atopic polygenic risk score is associated with paradoxical eczema developing in psoriasis patients treated with biologics

Based on the association data from this set of studies, I performed an exploratory analysis and tried to answer the following questions:

1. How many and what genetic variants (SNPs) have been found to be associated with the onset of psoriasis?

2. How many and what genes have been found to be associated with the onset of psoriasis?

3. What genes have the largest number of SNPs associated with the onset of psoriasis?

So, let’s try to answer these questions: 

How many and what genetic variants (SNPs) have been found to be associated with the onset of psoriasis?

In total, there were 54 SNPs that have been reported to be associated with psoriasis. 

Out of those 54 SNPs, there was only one SNP that appeared more than once, and that was rs2233278, which is located in the TNIP1 gene.  

The TNIP1 gene, also known as TNFAIP3 interacting protein 1, plays a crucial role in the immune system and the regulation of inflammation more specifically, it is known to have a role in the modulation of apoptosis. Details of the exact function of the TNIP1 gene are less clear, but it seems that its interaction with NF-kappaB suggests that it is involved in cell survival and death.

The other 53 SNPs are: rs2233278, rs9394026, rs34536443, rs4683946, rs3802826, rs2675669, rs12489120, rs10979182, rs62149416, rs2675662, rs7552167, rs694739, rs7709212, rs892085, rs9533962, rs9988642, rs1295685, rs17716942, rs181359, rs2066819, rs2700987, rs27432, rs28512356, rs28998802, rs33980500, rs4685408, rs367569, rs4712528, rs4406273, rs4845454, rs610604, rs11795343, rs7536201, rs4561177, rs7637230, rs1056198, rs10865331, rs12445568, rs1250544, rs12884468, rs1050414, rs6672420, rs1177203, rs2312786, rs74817271, rs12188300, rs9481169, rs6933987, rs2249937, rs12212594, rs34725611, rs192705221, rs72925168.

How many and what genes have been found to be associated with the onset of psoriasis?

Out of those 53 unique SNPs associated with psoriasis, 20 are not located in any specific gene but rather in intergenic regions, while remaining 33 SNPs are located in the following genes: TNIP1, RNF114, UBE2L3, ERAP1, TH2LCRR, IL13, KCNH7, CAMK2G, LINC02571, ETS1, ELMO1, STX1B, TYK2, MUC22, SLC1A2, RDUR, REL-DT, RMI2, TRAF3IP2-AS1, TRAF3IP2, STAT2, CDKAL1, BHLHE40-AS1, TNFAIP3, QTRT1, NOS2, RDX, ZMIZ1, PLCL2, PLCL2, RUNX3, HLA-C, HLA-C, HLA-C, HLA-C, HLA-C, HLA-C, RIGI

What genes have the largest number of SNPs associated with the onset of psoriasis?

The following genes have two or more SNPs highly associated with psoriasis:

1. The gene with largest number of SNPs (three) is the TNIP1 gene with following three SNPs: rs2233278, rs2233278, rs74817271

2. The next two genes are: REL-DT harboring SNPs:  rs62149416 and rs1177203 and the gene TYK2 harboring SNPs: rs34536443 and rs34725611

3. If we look for intergenic regions, then there are two SNPs , rs7709212 and rs12188300 that are located between the IL12B and LINC01845 genes. 

4. Also, between the NFKBIZ and RDUR genes, there are: rs4683946 and rs2312786.

So, Is Psoriasis Hereditary?

Well, from what I already wrote, it is obviously that psoriasis is strongly determined by genetics. Still, the nature of the heredity of psoriasis is not simply Mendelian, like how the color of eyes or hair color is inherited, where a relatively simple inheritance chart can be drawn. Psoriasis is, as we already mentioned, a complex genetic condition that is determined by many genetic variants, and therefore, the exact inheritance pattern is complex to determine. However, one can try to assess genetic predisposition toward psoriasis using available genetic data, and this is where if you have 23andMe can give you some insight. 

What 23andMe Raw Genotype Data Can Tell Us About Our Risk For Psoriasis?

If you did the 23andMe genetic test, you can download the raw genotype data, containing genotype information for over half a million SNPs that 23andMe assesses to produce its results. Now, you can use that information to get insights into your potential genetic predisposition to psoriasis.

For this purpose, I checked how many of those 53 SNPs associated with psoriasis are present in my 23andMe raw genotype data and made a short report.

So, out of those 53 SNPs highly associated with psoriasis, 21 SNPs were available in my 23andMe raw genotype data.

SNP	Gene(s) or intergenic region	Risk allele	My genotype
rs12188300	IL12B - LINC01845	T	AA
rs12884468	PSMA6 - RPLP0P3	G	CT
rs2233278	TNIP1	C	GG
rs2233278	TNIP1	C	GG
rs33980500	TRAF3IP2-AS1, TRAF3IP2	T	CC
rs4406273	LINC02571	A	GG
rs4685408	PLCL2, PLCL2	G	--
rs72925168	SLC1A2	G	AA
rs10865331	RN7SL51P - RN7SL18P	A	AG
rs11795343	RIGI	T	CT
rs181359	UBE2L3	A	AG
rs2675662	CAMK2G	A	AG
rs28512356	TP63 - P3H2	C	AC
rs7637230	RDUR	A	AG
rs7709212	IL12B - LINC01845	T	CT
rs892085	QTRT1	A	AG
rs17716942	KCNH7	T	TT
rs2249937	TAGAP-AS1 - FNDC1-AS1	G	GG
rs34536443	TYK2	G	GG
rs610604	TNFAIP3	G	GG
rs9533962	LINC00407 - LINC00330	C	CC
rs9988642	IL23R - RNU4ATAC4P	T	TT

Based on the genotype results from 23andMe data (based on those 22 available SNPs), we could say that I have slightly increased predisposition toward psoriasis. To explain again the color coding:

1. Orange means that genotype with no effect alleles. So, no positive effect, and we don't have any alleles with negative effects. So, we will consider these genotypes as population averages.

2. Light red means that the genotype has one effect allele, and assuming an additive genetic model it has a positive effect, but not like genotypes with two effect alleles.

3. Dark red means that the genotype has both effect alleles, and assuming an additive genetic model, it has a double positive effect compared to genotypes with only one positive effect allele.

Also, I have to underline again and say that this is based only on those 22 highly significant SNPs. You can use your 23andMe raw data and do the same thing for yourself. If you want, drop me a message, and I will do it for you for free.