Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted.

OBJECTIVE: The objective of this research paper is to search for rare genetic MS risk variants in the genetically homogenous population of the isolated Faroe Islands.

METHODS: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by-descent shared segments using the PLINK-program.

RESULTS: A segment spanning 63 SNPs with excess case-case-pair sharing was identified (0.00173 < p > 0.00212). A haplotype consisting of 42 of the 63 identified SNPs which spanned the entire the Sortilin-related vacuolar protein sorting 10 domain containing receptor 3 (SORCS3) gene had a carrier frequency of 0.34 in cases but was not present in any controls (p = 0.0008).

CONCLUSION: This study revealed an oversharing in case-case-pairs of a segment spanning 63 SNPs and the entire SORCS3. While not previously associated with MS, SORCS3 appears to be important in neuronal plasticity through its binding of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis.

Original languageEnglish
JournalMultiple Sclerosis Journal
Volume22
Issue number6
Pages (from-to)733-740
ISSN1352-4585
DOIs
Publication statusPublished - 2016

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Denmark
Single Nucleotide Polymorphism
Haplotypes
Genome-Wide Association Study
Glutamic Acid
Homeostasis
Research
Population

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@article{1c9308c6990f46ccb9fc05e127fe386a,
title = "Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene",
abstract = "BACKGROUND: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted.OBJECTIVE: The objective of this research paper is to search for rare genetic MS risk variants in the genetically homogenous population of the isolated Faroe Islands.METHODS: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by-descent shared segments using the PLINK-program.RESULTS: A segment spanning 63 SNPs with excess case-case-pair sharing was identified (0.00173 < p > 0.00212). A haplotype consisting of 42 of the 63 identified SNPs which spanned the entire the Sortilin-related vacuolar protein sorting 10 domain containing receptor 3 (SORCS3) gene had a carrier frequency of 0.34 in cases but was not present in any controls (p = 0.0008).CONCLUSION: This study revealed an oversharing in case-case-pairs of a segment spanning 63 SNPs and the entire SORCS3. While not previously associated with MS, SORCS3 appears to be important in neuronal plasticity through its binding of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis.",
author = "Stefanie Binzer and Egon Stenager and Michael Binzer and Kyvik, {Kirsten Ohm} and Jan Hillert and Kerstin Imrell",
note = "{\circledC} The Author(s), 2015.",
year = "2016",
doi = "10.1177/1352458515602338",
language = "English",
volume = "22",
pages = "733--740",
journal = "Multiple Sclerosis Journal",
issn = "1352-4585",
publisher = "SAGE Publications",
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}

Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene. / Binzer, Stefanie; Stenager, Egon; Binzer, Michael; Kyvik, Kirsten Ohm; Hillert, Jan; Imrell, Kerstin.

In: Multiple Sclerosis Journal, Vol. 22, No. 6, 2016, p. 733-740.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene

AU - Binzer, Stefanie

AU - Stenager, Egon

AU - Binzer, Michael

AU - Kyvik, Kirsten Ohm

AU - Hillert, Jan

AU - Imrell, Kerstin

N1 - © The Author(s), 2015.

PY - 2016

Y1 - 2016

N2 - BACKGROUND: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted.OBJECTIVE: The objective of this research paper is to search for rare genetic MS risk variants in the genetically homogenous population of the isolated Faroe Islands.METHODS: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by-descent shared segments using the PLINK-program.RESULTS: A segment spanning 63 SNPs with excess case-case-pair sharing was identified (0.00173 < p > 0.00212). A haplotype consisting of 42 of the 63 identified SNPs which spanned the entire the Sortilin-related vacuolar protein sorting 10 domain containing receptor 3 (SORCS3) gene had a carrier frequency of 0.34 in cases but was not present in any controls (p = 0.0008).CONCLUSION: This study revealed an oversharing in case-case-pairs of a segment spanning 63 SNPs and the entire SORCS3. While not previously associated with MS, SORCS3 appears to be important in neuronal plasticity through its binding of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis.

AB - BACKGROUND: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted.OBJECTIVE: The objective of this research paper is to search for rare genetic MS risk variants in the genetically homogenous population of the isolated Faroe Islands.METHODS: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by-descent shared segments using the PLINK-program.RESULTS: A segment spanning 63 SNPs with excess case-case-pair sharing was identified (0.00173 < p > 0.00212). A haplotype consisting of 42 of the 63 identified SNPs which spanned the entire the Sortilin-related vacuolar protein sorting 10 domain containing receptor 3 (SORCS3) gene had a carrier frequency of 0.34 in cases but was not present in any controls (p = 0.0008).CONCLUSION: This study revealed an oversharing in case-case-pairs of a segment spanning 63 SNPs and the entire SORCS3. While not previously associated with MS, SORCS3 appears to be important in neuronal plasticity through its binding of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis.

U2 - 10.1177/1352458515602338

DO - 10.1177/1352458515602338

M3 - Journal article

C2 - 26362888

VL - 22

SP - 733

EP - 740

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

IS - 6

ER -