형제 및 자매의 유전자형 자료에 기초한 전달불균형 검정법에 관한 연구

김진흠,장양수,Kim, Jin-Heum,Jang, Yang-Soo 한국통계학회 2008 응용통계연구 Vol.21 No.1

Family-based tests such as the transmission and disequilibrium tests(TDT) have proved to be powerful tools in the search for disease genes. Unlike case-control studies, the tests are not affected by population admixture, which can lead to spurious association of multiple highly linked makers with disease-susceptible genes. Those tests have largely required knowledge of parental marker genotypes. However, parental data are often not available for late-onset diseases. In this article we propose sib-TDTs that overcome this problem by use of marker data from unaffected sib(s) instead of parents. To do this end, we fist defined a Mantel-Haenszel-type statistic for each haplotype and then proposed two tests based on this statistic. Simulation studies suggest that the proposed tests are robust to population admixture and are monotone increasing as a relative risk increases irrespective of mode of inheritance. We also illustrated the proposed tests with data adopted from Yonsei Cardiovascular Genome Center. 전달불균형 검정법(transmission and disequilibrium test)과 같은 가계중심(family-based) 검정법들은 질병 관련 유전자를 찾는 데 매우 유용한 방법으로 알려져 있다. 사례-대조군 연구와 달리 가계중심 검정법들은 집단혼합(population admixture)으로 인한 영향을 받지 않기 때문에 질병 관련 유전자와 표지자(marker) 사이의 집단 혼합으로 인한 가짜 연관성(spurious association)에 노출될 위험이 없다. 가계중심 검정법들은 대체로 표지자에 대한 부모의 유전자형(genotype) 정보를 필요로 한다. 그러나 고령층에서 발병하는 질병의 경우에는 발단자(proband) 부모의 유전자형을 구할 수 없는 상황에 종종 마주치게 된다. 본 논문에서는 이런 어려움을 극복하기 위해 부모의 유전자형 대신 질병에 노출되지 않은 발단자 형제나 자매의 유전자형을 이용한 검정법을 제안하고자 한다. 이를 위해 먼저 가능한 모든 일배체형(haplotype)에 대해 Mantel-Haenszel 형태의 통계량을 정의하고 그것에 기초한두 가지 검정통계량을 제안하였다. 모의실험 결과, 제안한 검정법은 집단 혼합으로부터 로버스트하고 유전 양식(mode of inheritance)에 관계 없이 상대위험(relative risk)이 증가함에 따라 단조적으로 증가하는 검정력을 갖는 것으로 나타났다. 제안한 검정법을 연세대학교 심혈관계질환 유전체연구센터로부터 수집한 자료에 적용하고 그 결과를 고찰하였다.

종속적인 중도절단을 가진 동물종양 자료의 분석을 위한 모형

김진흠,김윤남,Kim, Jin-Heum,Kim, Youn-Nam 한국통계학회 2010 응용통계연구 Vol.23 No.5

동물종양 실험에서는 종양발생 시간이 직접 관찰되지 않고 단지 자연사로 인한 관찰 시점이나 강제적으로 희생시킨 시점 이전에 종양이 발생했는지 유무만을 알 수 있다. 이와 같은 형태의 결측을 가진 자료를 분석하기 위해 3단계(건강$\rightarrow$종양발생$\rightarrow$사망) 모형이 널리 사용되고 있다. 본 논문에서는 자연사로 인한 사망 시간이 종속적인 중도절단으로 작용하여 사망 시간과 종양발생 시간이 종속될 때, 이를 모형에 반영하기 위해 감마 프레일티 효과를 도입하였다. 모수 추정은 종양발생 시간과 프레일티 효과의 결측을 다루기 위해 EM 알고리즘 방법을 사용하였다. 제안한 추정량의 소표본 성질을 살펴보기 위해 제안한 방법을 Lindsey와 Ryan (1993, 1994)의 방광암 자료에 적용하여 모수를 추정하였으며, 그 추정값을 바탕으로 모의실험을 수행하였다. In animal tumorigenicity data, the occurrence time of tumor is not observed because the existence of a tumor is examined only at either time of natural death or time of sacrifice for the animal. A three-state model (Health-Tumor onset-Death) is widely used to model the incomplete data. In this paper, we employed a frailty effect into the three-state model to incorporate the dependency of death on tumor occurrence when the time of natural death works as an informative censoring against the tumor onset time. For the inference of parameters, then the EM algorithm is considered in order to deal with missing quantities of tumor onset time and random frailty. The proposed method is applied to the bladder tumor data taken from Lindsey and Ryan (1993, 1994) and a simulation study is performed to show the behavior of the proposed estimators.

기간분석에 따른 수정된 누적한계 추정량

김진흠,안윤옥,Kim, Jin-Heum,Ahn, Yoon-Ok 한국통계학회 2006 응용통계연구 Vol.19 No.3

임상시험 연구나 역학 연구에서 환자들의 예후는 흔히 생존을 추정을 통해 수량화 되곤 한다. 하지만 코호트 분석이나 완전분석에 의한 생존율 추정량들은 수년 전에 진단된 환자에 크게 의존하기 때문에 실제 생존율보다 더 낮게 추정하곤 한다. 본 연구에서는 최근의 생존정보를 잘 반영하는 생존을 추정을 위해 기간분석 방법을 통한누적한계 추정량을 제안하였고, 그 방법을 1993년 1월-1997년 12월 사이에 조사된 서울시 암등록 자료(Ahn등, 2002)에 적용하여 결과를 고찰하였다. Long-term survival rates are the most commonly used outcome measures for patients with cancer. However, traditional long-term survival statistics, which are derived by cohort analysis or complete analysis, essentially reflect the survival expectations of patients diagnosed many years ago. They are often outdated at the time they become available. In this article, we propose a modified product-limit method to obtain up-to-date estimates of long-term survival rates via a period analysis. The proposed method is illustrated with cancer registry data collected from January 1993 to December 1997.

환자-대조군 연구에서 인구집단 층화가 일배체형 경향성 검정에 미치는 영향

김진흠,강대룡,임현선,남정모,Kim, Jin-Heum,Kang, Dae-Ryong,Lim, Hyun-Sun,Nam, Chung-Mo 한국통계학회 2009 응용통계연구 Vol.22 No.5

Population stratification can cause spurious associations between genetic markers and disease locus. In order to handle this population stratification in haplotype-based case-control association studies, we added population indicators as covariates to the haplotype trend regression model proposed by Zaykin et al. (2002). We investigated through simulations how both population stratification and measurement error in the estimation of true population of each individual affect type I error probabilities of the association tests based on both Zaykin et al.'s (2002) model and the proposed model. Based on those results, in the situation that there exists population stratification but there is no error in population classification of each individual, our proposed model does satisfy a type I error probability whereas Zaykin et al.'s (2002) model does not. However, as the measurement error increases, a type I error probability of our model correspondingly becomes larger than a nominal significance level. It implies that as long as uncertainty in the estimation of true population of each individual still remains, it is nearly impossible to avoid false positive in case-control association studies based on haplotypes. 환자-대조군 연관성 연구에서 후보 유전자와 질병이 연관되어 있지 않더라도 인구집단 층화로 인해 가짜 연관성이 발생할 수도 있다. 본 연구에서는 일배체형에 기초한 환자-대조군 연관성 연구에서 인구집단 층화로 인한 가짜 연관성을 해결하기 위한 방법으로, Zaykin 등 (2002)이 제안한 일배체형 경향성 모형에 인구집단 층화에 대한 정보를 추가하고자 한다. Zaykin 등 (2002)의 모형과 제안한 모형에 기초한 일배체형의 유의성 검정에서 인구집단 층화와 인구집단에 대한 관측 오차가 제1종 오류율에 미치는 영향을 모의실험을 통해 살펴보았다. 인구집단이 층화되어 있지만 각 개체가 속한 인구집단을 정확히 알 수 있을 때, Zaykin 등 (2002)의 모형에 기초한 검정은 제1종 오류율을 잘 조절하지 못했지만 본 연구에서 제안한 모형에 기초한 검정은 제1종 오류율을 잘 조절하는 것으로 나타났다. 그러나 인구집단이 층화되어 있고 관측 오차가 존재하면 제안한 모형에 기초한 검정도 제1종 오류율을 조절하지 못하고 명목 유의수준보다 큰 값을 갖는 것으로 나타났다. 따라서 단일염기다형성에 기초한 환자-대조군 연관성 연구와 마찬가지로 일배체형에 기초한 환자-대조군 연관성 연구에서도 인구집단 층화에 대한 정보를 갖고 있다할지라도 그 속에 관측 오차가 존재하면 위양성을 피하기 어렵다는 것을 알 수 있었다.

일배체형에 기초한 연쇄분석의 통계학적 알고리즘 연구

김진흠,강대룡,이윤경,신선미,서일,남정모,Kim, Jin-Heum,Kang, Dae-Ryong,Lee, Yun-Kyung,Shin, Sun-Mi,Suh, Il,Nam, Chung-Mo 대한예방의학회 2004 예방의학회지 Vol.37 No.4

Objectives : This study was conducted to propose a new transmission/disequilibrium test(TDT) to test the linkage between genetic markers and disease-susceptibility genes based on haplotypes. Simulation studies were performed to compare the proposed method with that of Zhao et al. in terms of type I error probability and powers. Methods : We estimated the haplotype frequencies using the expectation-maximization(EM) algorithm with parents genotypes taken from a trio dataset, and then constructed a two-way contingency table containing estimated frequencies to all possible pairs of parents haplotypes. We proposed a score test based on differences between column marginals and their corresponding row marginals. The test also involved a covariance structure of marginal differences and their variances. In simulation, we considered a coalescent model with three genetic markers of biallele to investigate the performance of the proposed test under six different configurations. Results : The haplotype-based TDT statistics, our test and Zhao et al.'s test satisfied a type I error probability, but the TDT test based on single locus showed a conservative trend. As expected, the tests based on haplotypes also had better powers than those based on single locus. Our test and that of Zhao et al. were comparable in powers. Conclusion : We proposed a TDT statistic based on haplotypes and showed through simulations that our test was more powerful than the single locus-based test. We will extend our method to multiplex data with affected and/or unaffected sibling(s) or simplex data having only one parent s genotype.

1967년 군산·옥구 국회의원 선거의 부정행위와 지역사회에 미친 영향

김진흠 ( Kim Jin-heum ) 전남대학교 호남학연구원 2022 호남학 Vol.- No.72

1967년 제7대 국회의원 선거는 극심한 부정선거였다. 이는 군산·옥구 지역구의 선거에서도 확인할 수 있다. 선거운동 과정과 투·개표 과정에서 부정행위가 심했고, 특히 섬지역의 선거에서 많은 문제가 발생했다. 선거운동 과정에서는 대통령과 고위관료들이 군산에 내려와 금강을 가로질러 전북 군산과 충북 서천을 연결하는 군산대교를 건설하겠다며 기공식까지 치르는 등의 기만적인 허위공약을 남발했다. 선거 결과 전통적인 야당 강세 지역인 군산·옥구 선거구에서 야당인 신민당의 김판술 후보가 근소한 차이로 낙선했고, 여당인 민주공화당의 차형근 후보가 당선되었다. 선거 결과가 발표된 직후 전국적으로 부정선거에 대한 시위가 이어졌다. 박정희 대통령은 군산·옥구 선거구의 차형근을 포함한 6명의 당선자와 1명의 낙선자를 공화당에서 제명할 수밖에 없었는데, 이는 부정선거를 시인한 것이나 마찬가지였다. 혼탁한 선거에서 비롯된 피해는 지역민의 몫이었다. 헛된 공약에 속아서 과거의 영광을 기대하며 원치 않았던 후보에게 투표하고, 혹은 부정선거로 인해 원하지 않는 지역대표를 떠안게 되었던 지역민들은 선거 이후 군산·옥구가 부정선거의 대표 지역으로 거론되면서 논란의 중심에 서는 불명예까지 얻게 되었다. 부정선거에 대해 항의하고 투쟁하여 바로잡는 것도 결국 지역민의 몫이었다. 군산·옥구 지역은 이전부터 민주화운동이 적극적으로 일어났던 지역이었다. 군산의 지역민들은 1967년 부정선거 규탄투쟁에 나섰다. 부정선거와 허위공약에 시달리며 실질적인 피해자였던 군산·옥구 지역민들은 직접 시위에 나서 부정에 항의하고 상황을 바로잡으려 했다. 그 과정에서 일어난 ‘신민당사 난입사건’과 신민당 대변인 김대중의 ‘중대 사태’ 발언 등은 군산에서의 시위가 특별했다는 것을 보여준다. 그런 면에서 군산·옥구의 부정선거 규탄 시위는 전국적인 부정선거 반대운동에 하나의 동력을 제공하는 역할을 했다고 볼 수도 있다. 이와 같은 점들을 통해 1967년 군산·옥구 국회의원 선거의 역사적 의의와 중요성을 찾을 수 있고, 그동안 잘 알려지지 않았던 지역사회의 역동적인 면모를 발견할 수 있을 것이라 생각한다. The 7th National Assembly election in 1967 was a severe rigged election. This can also be confirmed in the elections of Gunsan and Okgu districts. Cheating was severe in the election campaign process and voting and counting process, and many problems occurred especially in the elections in the island area. During the election campaign, the president and high-ranking officials made false promises, including a groundbreaking ceremony, saying they would build Gunsan Bridge across the Geumgang River to connect Gunsan, North Jeolla Province, and Seocheon, North Chungcheong Province. As a result of the election, Kim Pan-sul of the opposition New Democratic Party was defeated by a narrow margin in Gunsan and Ok-gu constituencies, which are traditionally strong opposition parties, and Cha Hyung-geun of the ruling Democratic Republican Party was elected. Immediately after the election results were announced, protests over rigged elections continued across the country, and President Park Chung-hee was forced to expel six elected and one unsuccessful candidate, including Cha Hyung-keun, from the Republican Party, equivalent to admitting rigged elections. The direct damage from the murky election was on the local people. Local people, who were deceived by false promises and voted for unwanted candidates in anticipation of past glory, or who were led by fraudulent elections, were disgraced at the center of controversy as Gunsan and Okgu were mentioned as representative areas of fraud after the election. It was ultimately up to the local people to protest and fight and correct this. Gunsan and Okgu areas, which were traditional opposition areas, have been areas where democratization movements have been actively taking place. Local people in Gunsan began a protest against the 1967 election fraud. The “New Democratic Party invasion incident” that took place in the process and the remarks of New Democratic Party spokesman Kim Dae-Jung on the “significant incident” show that the protests in Gunsan were special. Local residents in Gunsan and Okgu, who were actual victims of fraudulent elections and false pledges, staged a demonstration to protest the injustice and try to correct the situation. Through these points, the historical significance and importance of the 1967 Gunsan-Okgu National Assembly election can be found, and the dynamic aspect of the community can be found.

제1공화국 시기 민주당의 내각책임제 개헌 정책과 ‘민주주의 정당’ 위상의 획득

김진흠(Kim, Jin Heum) 한국동양정치사상사학회 2020 한국동양정치사상사연구 Vol.19 No.1

1955년 창당한 민주당은 창당 과정부터 내각책임제를 가장 중요한 정책으로 정했고, 이를 이승만 정권과의 가장 큰 차별 요소로 내세웠다. 민주당의 내각책임제 개헌주장은 민주당을 대표하는 정책이었다. 민주당은 내각책임제 개헌을 정책으로 표방했지만, 실제로는 개헌안을 구체적으로 제시하지 않았고 실행 의지도 뚜렷하지 않았다. 당의 간판으로 내각책임제를 내걸 때도 있었지만, 철저히 숨기는 경우도 있었다. 특히 민주당 내의 분파인 신파와 구파는 내각책임제를 대하는 태도에서 큰 차이가 있었다. 민주당은 독재의 근원을 ‘우리 실정에 맞지 않는 대통령중심제’에서 찾았고, 독재를 막기 위해서는 내각책임제 개헌이 필요하다고 주장했다. 즉 사람이 아닌 제도에서 문제를 찾고 있었다. 민주당에서는 내각책임제는 민주적 제도이며, 그 대척점에 있는 이승만 정권의 대통령중심제는 반민주적인 제도라고 선전했다. 내각책임제 개헌을 통해 민주주의를 회복할 것이라 주장했다. 그러나 내각책임제는 그들의 구호처럼 민주주의 달성을 위한 유일한 정치적 제도가 아니었다. 또한 민주당에게 있어 내각책임제로의 개헌 정책은 집권을 위해서는 버릴수도 있는 선전적 성격이 강한 것이었다. 그렇기 때문에 민주당의 내각책임제 정책은 그 구체적인 내용이 수시로 달라졌고, 개헌에 대한 태도도 일정하지 않았다. 민주당의 내각책임제 정책은 내부를 결속하고 반독재를 외치는 구호적 성격이 강했다. 그럼에도 민주당은 야당으로서의 투쟁 활동과 함께 내각책임제 개헌을 당의 대표 정책이자 공약으로 내세웠고, 그 과정에서 점차 ‘민주주의 정당’으로서의 위상을 획득할 수 있었다. The Democratic Party, which was founded in 1955, has set the Cabinet responsibility system as the most important policy from the start of its founding, and has put it up as the biggest difference from the Rhee administration. The DP’s call for a constitutional revision of the parliamentary cabinet system was a policy that represented the DP. The Democratic Party advocated a constitutional revision of the parliamentary cabinet system as a policy, but in reality it did not provide a specific proposal for a constitutional revision and it did not have a clear will to implement it. There have been times when the party proposed a cabinet responsibility system as a front of the party, but there have been cases where it has been completely hidden. In particular, the New Faction and the Old Faction within the DP differed greatly in their attitude toward the cabinet system. The Democratic Party claimed that it found the source of dictatorship in a “presidential-centered system that does not fit our situation,” and that a constitutional revision of the parliamentary responsibility system is necessary to prevent dictatorship. In other words, they were looking for problems in the system, not in people. But the Cabinet-responsibility system was not the only political system for achieving “democracy,” the constitutional revision of the parliamentary responsibility system was a highly propaganda policy that could be abandoned for the sake of power. That is why the DP’s policy on the parliamentary cabinet system has changed its specifics from time to time. The DP’s Cabinet-responsibility policy was strong in its slogan of “uniting the inside and calling for anti-dictatorship.” In this process, the DP was able to acquire its status as a “democratic party” by insisting on a constitutional revision of the parliamentary responsibility system.

1950년대 이승만 대통령의 "불교 정화" 유시와 불교계의 정치 개입

김진흠 ( Jin Heum Kim ) 수선사학회 2015 史林 Vol.0 No.53

President Syngman Rhee announced the ``Buddhist Purification`` instructions a total of seven times from May 2, 1954 to Dec 8, 1955. This presidential instructions made conflict between the married Buddhist priests and the single Buddhist monks explode. Syngman Rhee regarded Buddhist temple as cultural asset or tourist attraction. And he didn``t consider religious concern and the internal conflicts of Buddhist. In the process of the ``Buddhist Purification``, the married Buddhist priests were determined as the ``pro-Japanese collaborators``. Syngman Rhee repeatedly emphasized that the married Buddhist priests have done pro-Japanese activities. Anti-Japanism used at the ``Buddhist Purification`` Instructions was periodical feature. During that time, Syngman Rhee emphasized ``anti-Japanism`` throughout the society. Anti-Japanism was applied to ``Buddhist Purification`` Instructions as Syngman Rhee intended. After presidential Instructions, the Buddhist ``Purification Movement`` couldn``t be compromised because of the government intervention. The married Buddhist priests and the single Buddhist monks just fought for interests, and depended on the government power than compromise. Their conflicts finally led to lawsuits. In the process of the Buddhist ``Purification Movement``, the Buddhists had close relationship with the government to receive help from the governmental authority. The illegal pro-government election campaign of the single Buddhist monks in the 1950s is a well-known fact. According to the documents, the married Buddhist priests were as well. The married Buddhist priests systematically supported the Liberal official candidates in the 4th National Assembly Election on May 2, 1958. Although Syngman Rhee firmly excluded the married Buddhist priests, they didn``t have a choice but to support Syngman Rhee government and the Liberal Party to survive.

1958년 5·2총선 연구 -부정 선거를 중심으로-

김진흠 ( Jin Heum Kim ) 수선사학회 2013 史林 Vol.0 No.44

In the 4th National Assembly election on May 2nd, 1958, the ruling party won a landslide victory at the rural areas, and the opposition party won at the urban areas. However this was not reflected differences of political awareness between urban areas and rural areas, but a greater or lesser degree by the election frauds. The election frauds had appeared all the elections under Syng-man Rhee regime. But there were distinctions among them. The 1st National Assembly election in 1948 and the 2nd National Assembly election in 1950 appeared obstruction of candidacy and suppression of election campaign. The targets of suppression were mostly Rhee`s political opponents and celebrities. In the 3rd National Assembly election in 1954, election frauds were also rife in the process of candidacy and election campaign. But illegality in the process of vote and vote counting had not yet been revealed. On the other hand, the 3rd presidential election in 1956 was widely known as a fraudulent election in the process of the vote counting. Despite the corruption of the vote counting, Bong-am Cho, the Progressive presidential candidate, put up a good fight, and Myon Chang, the Democratic vice presidential candidate, won the election. This was staggering news to Syng-man Rhee. Since then, intensified election frauds were entirely committed all the following elections. As a preliminary Syng-man Rhee regime came to dominate the local election in August, 1956. And tightening the control of ``Koongminban``, government kept a close watch on nation. Before the 4th National Assembly election, through negotiations of election law, Rhee`s regime with the Democratic party discluded minor political parties as a donation system. The election law had a legal loophole article that election frauds were permitted within maintaining the election result. This article made against the opposition party in the course of the election cases. Despite the election frauds, the Democratic Party secured seats that could protect the constitution. The growth of the Democratic Party reflected hostility towards Rhee`s regime. There were many factors that the Democratic Party made a good fight at the election. Economic crisis, improvement in standards of politics from the expansion of education, enlargement of the press, and damaging political reverse of Rhee`s regime, these were favorable factors to Democratic Party. That was the same in rural areas as in unban areas. Therefore severe election frauds only can be explained that the ruling party won a landslide victory at the rural areas. Hostility to Rhee`s regime was ever widening, but Rhee`s regime could not accept the advices from each field and lessons of last elections. Endangered Syngman Rhee plainly ignored the law and couldn`t sit up press reports. By extreme measure on this crisis, Rhee`s regime enforced the election frauds at the reelection for the National Assembly and next presidential election in 1960, so they led to self-destruction.

제1공화국 시기 지방자치법 개정의 배경과 목적: 1956년 제2차 지방자치법 개정을 중심으로

김진흠 ( Jin Heum Kim ) 이화사학연구소 2014 梨花史學硏究 Vol.0 No.48

Implement of the local self-government was postponed by the demand of President Syngman Rhee. Syngman Rhee demanded appointment system at the selection of mayor of a city or town and headman of a village on the condition of implement of the local self-government. Under the trouble with the National Assembly, the local autonomy act was legislated in 1949. But the local election wasn``t implemented due to the Korean War. In 1952, with the Pusan Political Crisis just ahead, the first election of the local council was suddenly implemented. At this election, the ruling party took up about 60% of the seats and the independent members took up about 40% of the seats. The first local council members were mostly regarded as pro-government group. But they were also analyzed that they had a critical opinion without considering the party register. The first local council could exercise non-confidence resolution against a local government head. The government insisted that the local self-government had problems because the local council abused non-confidence resolution. This insistence of the government was based on the revision of local autonomy act. Frequent resignations of local government heads arose from fraudulent acts by the local government head, not from abuse of non-confidence resolution. The government brought up a problem of abuse of non-confidence resolution in order to curtail the authority of the local council. The government committed direct violence and pressure when the local council didn``t obey the intention of the government. In some cases, the executive members of the Liberal Party went down to provinces, and then interfered the selection of the local government head. The Police also forced the local council members to elect specific candidate by committing violence. After all, the Syngman Rhee regime implemented the second revision of local autonomy act in February 1956 which contained elimination of non-confidence resolution, so that authority of local council was highly reduced and the local government heads were subordinate to the government more intensively.