Genome-wide Association Study in a High-risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2010 Feb 18

PMID 20159113

Citations 107

Authors

Eveliina Jakkula

Virpi Leppa

Anna-Maija Sulonen

Teppo Varilo

Suvi Kallio

Anu Kemppinen

Shaun Purcell

Keijo Koivisto

Pentti Tienari

Marja-Liisa Sumelahti

Irina Elovaara

Tuula Pirttila

Mauri Reunanen

Arpo Aromaa

Annette Bang Oturai

Helle Bach Sondergaard

Hanne F Harbo

Inger-Lise Mero

Stacey B Gabriel

Daniel B Mirel

Stephen L Hauser

Ludwig Kappos

Chris Polman

Philip L De Jager

David A Hafler

Mark J Daly

Aarno Palotie

Janna Saarela

Leena Peltonen

Affiliations

Soon will be listed here.

Abstract

Genetic risk for multiple sclerosis (MS) is thought to involve both common and rare risk alleles. Recent GWAS and subsequent meta-analysis have established the critical role of the HLA locus and identified new common variants associated to MS. These variants have small odds ratios (ORs) and explain only a fraction of the genetic risk. To expose potentially rare, high-impact alleles, we conducted a GWAS of 68 distantly related cases and 136 controls from a high-risk internal isolate of Finland with increased prevalence and familial occurrence of MS. The top 27 loci with p < 10(-4) were tested in 711 cases and 1029 controls from Finland, and the top two findings were validated in 3859 cases and 9110 controls from more heterogeneous populations. SNP (rs744166) within the STAT3 gene was associated to MS (p = 2.75 x 10(-10), OR 0.87, confidence interval 0.83-0.91). The protective haplotype for MS in STAT3 is a risk allele for Crohn disease, implying that STAT3 represents a shared risk locus for at least two autoimmune diseases. This study also demonstrates the potential of special isolated populations in search for variants contributing to complex traits.

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