GWAS & lupus
Published in July 2017 in Nature Communications, a new GWAS study identified a number of genetic markers that contribute to the heredity of lupus. The number of genetic markers identified varied by ethnicity. The study was led by researchers at Wake Forest Baptist Medical Center, Oklahoma Medical Research Foundation, King’s College of London, and Genentech, Inc. Within the paper, it is noted that 3 of the researchers were employees of Genentech, Inc. but no other conflicts of interest were reported.
The lead author of the study, Dr. Carl Langefeld of Wake Forest School of Medicine said: “This study is the largest multi-ethnic lupus genetics study to date and allowed us to identify many new genetic markers, some of which are specific to individual ethnic groups and others that are shared across ethnicities.”
To evaluate the genetic data, this study used Immunochip genotype data. Immunochip is a “single-nucleotide polymorphism (SNP) microarray.” Additional information is available at the link via the NIH to learn more about SNPs. But, SNPs are used to identify inheritance of diseases that run in families. This allows for research into the heredity of lupus.
The study evaluated genetic variations in 3 different ancestral groups: European ancestry, African ancestry, and Hispanic Amerindian ancestry. The results varied by group. During the trial, three tiers of significance were used. For simplicity, we will combine the top two in the analysis below. The third will be excluded. In total, 58 genetic markers were identified, 24 of which had not previously been identified.
All result regions were independent of the Human Leukocyte Antigen (HLA) associations identified by previous studies, though the HLA regions were also examined by this study. In addition to the new regions identified, there were 2 important take aways from this research:
- “Nearly 50% of these regions had multiple genetic variations that predispose someone to lupus”
- It does not appear that the genetic variants work independently. This is because the risk of lupus increases more than expected as the number of genetic variations increases. That is to say, the risk does not increase linearly. Because of this, the authors of the study propose a “cumulative hits hypothesis for autoimmune disease”
There were also some important limitations to the study. The first is that there were considerably fewer non-European ancestry participants and controls. The second issue is that the Immunochip content has a strong European-ancestry bias due to when and how it was developed. The researchers noted that fewer SNP associations were found for African-ancestry participants than were expected based on power calculations.
Control participants: 11,516
Distinct regions identified: 58
Novel regions identified: 27
Control participants: 2,452
Distinct regions identified: 9
Novel regions identified: 4
Control participants: 2,016
Distinct regions identified: 16
Novel regions identified: 9