Ginns E I, St Jean P, Philibert R A, Galdzicka M, Damschroder-Williams P, Thiel B, Long R T, Ingraham L J, Dalwaldi H, Murray M A, Ehlert M, Paul S, Remortel B G, Patel A P, Anderson M C, Shaio C, Lau E, Dymarskaia I, Martin B M, Stubblefield B, Falls K M, Carulli J P, Keith T P, Fann C S, Lacy L G, Allen C R, Hostetter A M, Elston R C, Schork N J, Egeland J A, Paul S M
Clinical Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15531-6. doi: 10.1073/pnas.95.26.15531.
Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5. 22 x 10(-4); SIBPAL Pempirical value <3 x 10(-5)) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 x 10(-3); SIBPAL Pempirical value <1 x 10(-3)) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.
双相情感障碍（BPAD；躁郁症）的特征是躁狂发作和/或轻躁狂发作，其间穿插着抑郁期。有力证据支持遗传因素在BPAD易感性中起重要作用。然而，迄今为止，连锁研究仅试图确定导致或增加患BPAD风险的染色体位点。为了确定是否存在类似于其他遗传疾病中观察到的、可预防或降低患BPAD风险的保护性等位基因，我们在几个BPAD发病率极高的大型多代阿米什人谱系的全基因组连锁扫描中，将心理健康状况（无任何精神疾病）作为表型。我们发现，在4号染色体p臂上的D4S2949位点有强有力的证据（GENEHUNTER-PLUS最大非参数连锁分数 = 4.05，P = 5.22×10⁻⁴；SIBPAL经验性P值 < 3×10⁻⁵），在4号染色体q臂上的D4S397位点有提示性证据（GENEHUNTER-PLUS最大非参数连锁分数 = 3.29，P = 2.57×10⁻³；SIBPAL经验性P值 < 1×10⁻³）与心理健康状况相关。这些发现与某些等位基因可预防或改变BPAD及其他相关情感障碍临床表现的假说一致。
